Platform Presentations

THURSDAY OCTOBER 11, 10:30 a.m. – 12:00 p.m.



At the end of this session, participants will be able to:

  • Identify ongoing research around the country.
  • Communicate with colleagues from around the country.
  • Promote research collaboration.
  • Extend opportunities for members to discuss and examine research and clinical work in a supportive, collaborative environment.


Thursday, October 11, 10:30 – 10:45

OT01 Out-of-Province Genetic Testing: Experience of the CHU Ste-Justine Centralized Platform

VILLEMURE Frédéric, LABERGE Anne-Marie

Medical genetics, CHU Ste-Justine, Montréal

CHU Ste-Justine (CHUSJ) is designated as one of five approval centers for out-of-province genetic testing in Quebec. In 2012, a centralized approval platform was developed to standardize the approval process, in order to ensure that appropriate tests were selected and that costs were considered in test selection.

Objective: To describe the structure and review the activities of CHU Sainte-Justine’s Out-of-Province genetic testing platform since its creation in July 2012.

Methodology: Platform structure and procedures were reviewed. Using the platform database, we reviewed the number of tests performed per year, % of tests approved, tests most frequently ordered, and number of labs used.

Summary of Results: The platform involves 2 administrative assistants, a genetic counsellor and 4 medical geneticists. It is responsible for both administrative handling of test requests (approval, reimbursement, result tracking and report delivery) and physical handling of samples. It is the point of contact for healthcare professionals in our center and in referral centers regarding genetic testing, as well as for all communications with out-of-province laboratories. Prescribing physicians who submit a request for out-of-province testing must provide information about the patient (phenotype, previous testing, family history, rationale for testing) and the test they want to perform (e.g. genes to be covered, etc.). Every test request is reviewed and approved by a medical geneticist, who selects the specific test and laboratory to perform the test. Test requests have increased from about 1030 in 2013 to over 1700 test requests in 2017. Most of the increase in test requests is from non-geneticists. Although we reject only about 1% of test requests, the test selected is often different from the test requested, to better address the patient’s diagnostic needs. Because the platform is responsible for choosing the laboratory to perform the test, it ensures that, while quality and expertise of the different laboratories are always being considered, cost is also taken into account. A centralized platform also gives us an increased negotiation power with out-of-province laboratories.

Conclusions: Our centralized platform has made it easier for clinicians to order and track their tests. The platform has become an important information resource about genetic tests for clinicians in our center and in referral centers, helping to educate them about the appropriate use of genetic testing. Because of the volume of tests processed through the platform, we were able to provide feedback to out-of-province laboratories making it possible to get panels to meet our specific needs and deals on test prices. Because our approach is centralized but still based in the clinical setting, we think our approach could be valuable in other centers across Canada.


Thursday, October 11, 10:45 – 11:00

OT02 Study to Avoid cardioVascular Events in British Columbia (SAVE BC)

LYNCH Kelsey1, VIKULOVA Diana, NG, Phoebe, BROWN Chad, PIMSTONE Simon, BRUNHAM Liam

1University of British Columbia, Vancouver, BC.

Objective: Premature atherosclerotic cardiovascular disease (ASCVD) is common, highly heritable and genetically complex. In British Columbia (BC) each year, approximately 750 men ≤50 and women ≤55 years are diagnosed with ASCVD. Because first degree relatives (FDRs) of individuals with premature ASCVD are at increased risk of atherosclerosis, guidelines recommend screening of FDRs. Despite such recommendations, no structured mechanisms exist in BC for the identification and screening of such families. To address this gap, we established SAVE BC, a patient-oriented research program aimed at identifying and following index patients with very premature ASCVD and their FDRs and spouses.

Methods: Index patients are defined as men ≤50 and women ≤55 years with a ≥50% angiographically or radiographically defined stenosis in at least one coronary artery. SAVE BC currently recruits index patients at BC’s two largest academic medical centres. Index patients, FDRs and spouses are assessed by a medical specialist and are then provided genetic counselling by a certified genetic counsellor, who also manages the program. Saliva and/or blood samples are obtained for future genetic research studies. FDRs and spouses are offered one of three screening modalities for subclinical atherosclerosis: 1) carotid ultrasound, 2) coronary artery calcium score (CACS) or 3) coronary computed tomography angiogram (CCTA).

Summary of Results: SAVE BC began patient recruitment in December 2015. As of June 7, 2018, 324 index patients meeting our inclusion criteria have provided consent, as well as 164 FDRs and spouses. 16% of index patients have met clinical criteria for Familial Hypercholesterolemia, despite not having previously been diagnosed. For FDRs and spouses that have undergone screening, 44% of FDRs versus 24% of spouses have been identified as having subclinical atherosclerosis and therefore need to be treated to secondary prevention targets. Cascade and reverse cascade screening has allowed SAVE BC to identify FDRs of index patients who previously had not been screened, but through our program were found to have subclinical atherosclerosis.

Conclusion: SAVE BC, is a newly established patient-oriented research program of families with very premature ASCVD. Our initial results demonstrate the feasibility of implementing a structured program to identify high risk families with very premature ASCVD and of providing genetic counselling to these families. We expect that SAVE BC will identify numerous at-risk individuals in need of early intervention and ASCVD prevention, and ultimately help to reduce the burden of premature ASCVD in the province. In the longer term, the establishment of this unique patient cohort will help to elucidate the molecular and genetic factors that predispose to very premature ASCVD and will require additional genetic counsellors to aid in reporting on genetic risk in family members.


Thursday, October 11, 11:00 – 11:15

OT03 Return of raw clinical exome data in North America: Exploring laboratory policies and perspectives of healthcare providers

OSMOND Matthew1,2, CHAD Lauren1,2, CHITAYAT David1,2,3, MEYN Stephen4, BABUL-HIRJI Riyana1,2,5

1Department of Molecular Genetics, University of Toronto, Toronto, ON.
2Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON.
3Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON.
4Center for Human Genomics and Precision Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI.
5Department of Genetic Counselling, The Hospital for Sick Children

Introduction: Exome sequencing (ES) has rapidly become an integral part of clinical care in North America and has allowed for increased diagnostic yield in patients with non-specific phenotypes or previously negative genetic testing. Important areas for consideration that remain relatively unexplored in the literature include opinions of healthcare providers regarding the option of requesting/returning raw ES clinical data as well as the returning policies of laboratories. To address these existing gaps in knowledge, this study investigated current laboratory policies as well as perspectives of healthcare providers regarding the return of raw ES data.

Methods: Twenty North American laboratories were surveyed on their return policy of raw ES data by online document reviews and questionnaires completed by lab representatives, an approach that has been used in other studies when surveying practices across multiple clinical labs. To assess healthcare provider perspectives on the applications and limitations of raw ES, fourteen semi-structured interviews were conducted with clinicians (genetics and non-genetics) at The Hospital for Sick Children, who had experience with requesting ES testing. The transcripts were analyzed using a conventional content analysis. Patterns that emerged across multiple coded transcripts were grouped to form overarching themes.

Results: While many labs permitted the return of raw ES data to ordering providers, the consents required, data format, delivery method and cost varied significantly between each lab. Interviews with healthcare providers about the return of raw ES data revealed the following themes: (i) most raw data requests were healthcare provider-initiated for undiagnosed cases, (ii) healthcare provider concerns about handling raw data, including lack of expertise, (iii) patient-centric counselling considerations, including respecting patient ownership of their own medical data, and (iv) potential logistical challenges as requests for ES data increase.

Conclusion: The findings from this study will help to inform discussions in establishing best practice guidelines at both the institutional as well as at the professional organizational levels regarding the return and clinical use of raw WES data.


Thursday, October 11, 11:15 – 11:30

OT04 Reanalysis of clinical exome sequencing data under a research protocol results in diagnoses in both known and novel genes

ROJAS Samantha1, HARTLEY Taila1, GILLESPIE Meredith1, KERNOHAN Kristin1, ITO Yoko1, NAUMENKO Sergey2, BRUDNO Michael2, BOYCOTT Kym1 on behalf of the Care4Rare Canada Consortium3

1Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
2Centre for Computational Medicine and Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.

The introduction of exome sequencing (ES) into Clinical Genetics has revolutionized diagnostic care for patients with suspected monogenic disease and a broad differential diagnosis. However, the diagnostic rate of the now reported ~7,000 patients who have received this clinical test is only 25-35%. Patients may remain undiagnosed following ES for a multitude of reasons, including limitations of bioinformatics tools, sequencing strategy, and limitations in knowledge surrounding human genetic disease. In response to the large number of rare disease patients receiving ES as part of their clinical care, the Care4Rare (C4R) Canada Consortium created an ‘Unsolved Clinical Exome’ pipeline to enable the reanalysis of genetic data from clinical laboratories. Patients were recruited from 21 Clinical Genetics sites across Canada with C4R REB approval. In order to be included they had to have negative or indeterminate results from clinical ES, and provide free and informed consent for release and reanalysis of their ES data under a research protocol. Raw ES data was transferred from the original clinical laboratory to C4R’s secure server, and run through the C4R bioinformatics pipeline. Clinical information collected for the purpose of enabling the reanalysis included the original test details (clinical information provided, sequencing strategy and reported variants) and information provided by the ordering clinician (HPO terms). Here, we report the first 42 patients who had their raw ES data repatriated from 11 clinical laboratories and reanalyzed through the C4R pipeline. All cases were first reviewed for candidate variants in known disease genes associated with the patient’s HPO terms. From this primary analysis 3 cases (7%) had pathogenic or likely pathogenic variants identified. In one case, the variant was missed by the clinical laboratory. In the other two, novel information was available to support pathogenicity of the variant; in one case the gene had been recently identified to cause human disease, in the other the mutation had been recently reported hence bumping a VUS to likely pathogenic. Following analysis for known genes, we reviewed rare variants in the rest of the exome for the remaining 38 cases, with the intent of identifying novel gene-disease associations. Of these, 8 cases (19%) had novel candidates that we are pursuing through genetic validation and functional studies. An additional 23 cases (54%) had VUSs that require additional studies to resolve (e.g., ES of additional relatives, segregation). There is therefore significant utility in the reanalysis of clinical ES data in a research laboratory, resulting in both known and novel findings.


Thursday, October 11, 11:30 – 11:45

OT05 Exploring the Impact of Pharmacogenomic Results on Medical Management and Disclosure Behaviours

WALDMAN Larissa1,2, SHUMAN Cheryl1,2, COHN Iris3, KAISER Amy2, CHITAYAT David1,2, WASIM Syed4, HAZELL Allison5

1Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario.
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario.
3Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario.
4Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario.
5Medcan Health Management Inc, Toronto, Ontario.

Introduction: Pharmacogenomic (PGx) tests represent significant advances in precision medicine, allowing for the identification of genetic markers that better predict an individual’s response to a medication. Current literature includes studies that evaluate public opinions regarding PGx testing, as well as clinical and personal utility of general genetic tests. However, no study thus far has investigated the experiences and behavioural responses of individuals who underwent PGx testing, including pre- and post-test genetic counselling (GC).

Purpose: Explore participants’ perceptions following the return of PGx results, as well as their medication management and disclosure behaviours.

Methods: In November 2016, Medcan, a health and wellness clinic in Toronto, Ontario, began offering a PGx panel facilitated by a genetic counsellor. We surveyed clients who had PGx testing, including pre- and post-test GC. The survey included both quantitative and open ended response questions.

Results: The survey was emailed to 166 eligible participants, with a response rate of 22%. 84% of participants found pre-test GC helpful to both understanding the possible results and the purpose of testing; 94% found the post-test GC helpful in understanding their PGx results. 50% of participants disclosed their results to a physician, 6% disclosed to a pharmacist, and 68% shared their results with family members. Qualitative analysis of participants’ open ended responses regarding their overall experience with PGx testing identified three recurring themes: 1) psychological reassurance, 2) perceived utility: informative and useful versus confusing and not impactful, 3) experiences with disclosure to other healthcare providers.

Conclusion: Our study findings support the provision of pre- and post-test GC services for a non-disease related genetic test, and the importance of managing expectations surrounding PGx testing in pre-test GC. As well, GC should include discussion regarding disclosure of results with other members of the healthcare team, and at risk family members.


Thursday, October 11, 11:45 – 12:00

OT06 CffDNA testing in the context of ultrasound soft markers

DOUGAN, Shelley, BELLAI DUSSAULT, Kara, HUANG, Tianhua, WALKER, Mark, LANES, Andrea, OKUN, Nan, ARMOUR, Christine

Background: Ontario offers a publicly-funded contingent model of prenatal screening where cell-free fetal DNA (cffDNA) testing is funded in situations conferring a higher risk for fetal aneuploidy. One of the clinical indicators for funded cffDNA testing is a risk of aneuploidy greater than a screen positive serum result, where the risk can be modified by ultrasound factors, such as fetal anomalies or soft markers. The current clinical practice regarding soft markers and their inclusion in a patient’s risk assessment for fetal aneuploidy varies by clinic. The current Canadian guidelines recommend that certain soft markers, such as echogenic intracardiac focus and choroid plexus cysts should no longer be considered in the risk assessment and that their identification on ultrasound should no longer lead to further testing.1

Objectives: This study evaluated the value of cffDNA testing in the context of ultrasound soft markers by assessing the screen positive rates of publicly funded cffDNA testing for the indication of identification of ultrasound markers.

Methodology: This descriptive cohort study was based on the secondary analysis of data collected by Ontario’s prescribed maternal and child registry, the Better Outcomes Registry & Network (BORN), to which all laboratories and hospitals contribute. The study population includes all pregnant women who received cffDNA testing from January 2016 to December 2017.

Results: 25,204 cffDNA testing records were collected over the study period, with 68% of tests meeting the clinical eligibility criteria for public funding. 1,423 cffDNA tests were funded for the indication of a single soft marker. The most common soft markers were intracardiac echogenic focus/foci with a total of 407 cffDNA tests funded for this indication, followed by choroid plexus cyst(s) with a total of 346 and increased nuchal fold with 189 tests.

Positive rates for cffDNA tests funded following the identification of soft markers were 3% for absent/hypoplastic nasal bone, 1.1% for increased nuchal fold, 0.7% for intracardiac echogenic focus/foci, 0.7% for hyperechogenic bowel and 0.3% for choroid plexus cyst(s). Positive rates for cffDNA tests funded following the identification of soft markers were null for pyelectasis, short long bones and ventriculomegaly.

Cystic hygroma was also included in the category of ultrasound markers modifying the risk of aneuploidy. Out of 64 cffDNA tests with the indication of cystic hygroma, 22 were screen positive.

Conclusion: We will investigate the cytogenetic outcomes of these screen positive cffDNA tests through BORN registry data. This information will allow the reevaluation of the practice of modifying risk assessment of fetal aneuploidy based on ultrasound factors in the context of a publicly funded contingent prenatal screening model.

1Audibert F, De Bie I, Johnson JA, et al. No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes. J Obstet Gynaecol Canada. 2017. doi:10.1016/j.jogc.2017.01.032



FRIDAY OCTOBER 12, 8:30 a.m. – 10:00 a.m.


Friday October 12, 8:30 – 8:45

OF01 RareConnect: Connecting and engaging rare disease patients globally

OSMOND Matthew1, SILVA Amanda2, MANASE Dorin2, HARTLEY Taila1, Care4Rare Canada1, BOYCOTT Kym1, BRUDNO Michael2

1Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
2Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Surveys and focus groups with families affected by rare diseases have shown that living with a rare disease can be socially isolating. RareConnect is an established social networking site that brings together rare disease patients, caregivers, and advocacy organizations inside moderated, multi-language discussion groups. RareConnect was founded by EURORDIS in 2009, and has grown to over 34,000 users, and includes more than 900 patient advocacy organizations, and operates in 12 languages. Approximately 20-30 new users sign up per day and are given the option of joining any one of the 150 disease-specific communities, including a community for people without a diagnosis. These communities are managed by several full-time administrators and 388 volunteer moderators from patient advocacy organizations. The communities provide patients with a supportive and safe environment to ask questions, share experience, and interact with others with a similar condition.

Recently, RareConnect ownership was transferred from EURORDIS to Care4Rare Canada, providing new opportunities to increase the site’s value to patients and families, advocacy organizations, researchers, and clinicians. While the vision of the social platform ( will remain the same, we are currently working to enable research functionality for the benefit of the rare disease community. Soon, a MyStudies tab will be available to patients on the social platform that will link them to a secure research platform ( that will anonymously and securely connect them to research ethics board approved studies for which they are eligible. For clinicians and researchers, this will represent a new and powerful tool for conducting surveys and collecting longitudinal data.


Friday October 12, 8:45 – 9:00

OF02 Incidence and carrier frequency of Tay-Sachs disease in French-Canadians from Quebec: a retrospective analysis covering 24 years (1992-2015)

SILLON Guillaume1, ALLARD Pierre2, DRURY Stella1, DE BIE Isabelle1

1Division of Medical Genetics, Department of Medicine, McGill University Health Center, Montreal, Quebec.
2Division of Medical Genetics, Department of Pediatrics, Sainte-Justine Hospital, Montreal, Quebec.

Tay-Sachs disease (TSD) is an autosomal recessive neurodegenerative condition with highest prevalence among individuals of Ashkenazi-Jewish descent. In the non-Jewish population of the United States, the TSD carrier frequency was shown to be 1/277 or 1/300 based on biochemical carrier screening or the incidence of affected children, respectively. An increased incidence of infantile TSD was demonstrated in French Canadians from the Bas-St-Laurent and Gaspésie regions. Carrier frequencies were published for French Canadians of specific Quebec regions, or calculated from New-England populations with French-Canadian (FC) heritage. However, no accurate carrier frequency has so far been established for the entire Quebec FC population. An estimate of this carrier frequency is needed so that a rational approach to carrier screening may be developed.

Objective: The goal of the present study is to estimate the incidence and carrier frequency of infantile TSD in the general Quebec FC population.

Methods: We ascertained the total number of infantile TSD cases during the 1992-2015 period at the McGill University Health Center and the Sainte-Justine Hospital in Montreal, the two provincial reference centers where these patients would be evaluated and treated. Cases were only included if the affected individual was born in 1992 or later. A diagnosis of TSD is usually made before a child’s second birthday. Therefore, cases diagnosed after 2015 were excluded as all affected individuals born after 2015 would not necessarily have been diagnosed yet. Incidence of infantile TSD was calculated based on the number of births to mothers whose language of use was reported as French. This incidence was used as an estimate for the number of births of FC descent. Carrier frequency was deduced using the Hardy-Weinberg equation.

Results: Preliminary results show that 7 cases of TSD were diagnosed in Quebec between 1992 and 2015. Taking into account the number of births to mothers whose language of use was French, this corresponds to an incidence of 1/218 130 (95% confidence interval (CI): 1/542 420 to 1/105 852). This in turn corresponds to an estimated carrier frequency of 1/234 (CI: 1/369 to 1/163). In the same 24-year period, 1 case of TSD was diagnosed prenatally to a Quebec FC couple. If this case is included, the incidence of TSD in the FC population of Quebec is calculated as 1/190 863 (CI: 1/441 942 to 1/96 854) and the carrier frequency as 1/219 (CI: 1/333 to 1/156).

Conclusions: The carrier frequency of TSD among Quebec French-Canadians is slightly higher than that postulated for the Non Jewish population of the United States. This could be explained by founder effects that are specific to the Quebec population. Pathogenic variants specific to the FC population have actually already been characterized. This data could be used for public policy decision making regarding carrier screening for TSD in the FC population.


Friday October 12, 9:00 – 9:15

OF03 The attitudes and expectations of parents of young adults with intellectual disability (ID) towards the transition from paediatric to adult medical care


North York General Hospital, Toronto, Ontario.

Objectives: Adolescents with intellectual disability (ID) and their caregivers need well-coordinated services and support in their transition from paediatric to adult care. However, literature suggests many parents of young adults with ID are dissatisfied with the transition process and are reluctant for their children to leave their paediatric providers. Our study aims to survey caregivers of young adults with ID from a genetics clinic in Ontario on their needs and concerns regarding transition.

Methodology: We administered a questionnaire to 51 parents and caregivers of adolescents and young adults with ID seen at a Genetics clinic of a community hospital in Toronto, Ontario. Statistical analysis was performed to determine trends and statistical significance.

Summary of Results: We found that the biggest concerns parents and caregivers have towards transition include: adult doctors not knowing the history of their child and not familiar with the genetic condition their child has; and adult doctors having less time for each appointment. We also found that families that need to transition out of paediatrician are more interested in attending a transition clinic, compared with families that do not currently see a paediatrician. Transition topics that are most desired by parents and caregivers to be addressed include education and employment opportunities, therapy services, and financial planning.

Conclusion: Our study assessed parents’ and caregivers’ current attitudes towards transition and their perceived value of a transition clinic for young adults with ID. The findings in our study will assist genetics clinics in meeting the transitional needs for adolescents and young adults with ID.


Friday October 12, 9:15 – 9:30

OF04 Expectations, experiences, and perspectives of consanguineous couples attending preconception and prenatal genetic counselling

THAIN Emily1,2,3, SHUMAN Cheryl1,2,3, MILLER Kristen1,4, SAPPLETON Karen5, MYLES-REID Diane6, CHITAYAT David1,2,6, GIBBONS Clare1,4

1Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
2Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
3Department of Genetic Counselling, The Hospital for Sick Children, Toronto, ON, Canada.
4Genetics Program, North York General Hospital, Toronto, ON, Canada.
5Centre for Innovation and Excellence in Child and Family-Centred Care, The Hospital for Sick Children, Toronto, ON, Canada.
6Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, ON, Canada.

Introduction: Consanguinity, the union between two individuals who are related as second cousins or closer, is a deeply rooted and respected practice in many communities. Despite social and cultural benefits of consanguineous unions, offspring are at increased risk of having an inherited genetic condition or congenital anomaly. Increased awareness of these risks has led to greater demand for preconception and prenatal genetic counselling. However, little is currently known about patient expectations of and experiences with genetic counselling for this indication, or their perspectives on genetic services relevant to family planning, such as expanded carrier screening (ECS).

Objective: Our study aimed to gain insight into the perspectives of individuals who receive genetic counselling for consanguinity.

Methods: We completed telephone interviews with 13 individuals who had recently received preconception or prenatal genetic counselling for consanguinity. Using a semi-structured interview guide, we explored participants’ expectations for the genetic counselling session, experiences discussing family history and reproductive risks with the genetic counsellor, attitudes toward reproductive planning, and views on ECS. Interview transcripts were analyzed using an interpretive descriptive approach.

Results: Many participants reported mixed anticipatory emotions prior to the appointment and were hoping for reassurance through information tailored to them as a couple. Participants valued genetic counsellors as sources of information and support, which contributed to their motivation for and comfort in sharing family history information in the appointment. Relief, reassurance, and optimism were described after discussing reproductive risks in the context of a non-contributory family history. Furthermore, enhanced understanding of consanguinity-related risks provided clarity and a path forward regarding family planning and prenatal testing options. Many viewed self-pay ECS as a valuable way to understand personalized risks and provide reassurance beyond what the counsellor offered through analysis of family history. However, cost of testing and emotional impact of positive results were cited as barriers to accessing ECS services. Overall, participants would have preferred genetic counselling at an earlier stage of their relationship and recognized a need for wider information dissemination about the availability of genetics services for consanguinity.

Conclusion: Our findings support the personal utility of genetic counselling for consanguinity. Additionally, they demonstrate the need for increased visibility and access to genetics information, counselling, and testing relevant to this patient population.


Friday October 12, 9:30 – 9:45

OF05 The end of an odyssey: A collaborative genetic testing program for Pompe disease identifies patients with Pompe and other rare neuromuscular disorders

HODSON Katherine1, PINHO Stéphanie1, POUCHET Carly1, JACOB Karine1, GANOPOLSKY Jorge1, THURIOT Fanny2, GRAVEL Elaine2, MARCOUX Lydia2, GRAVEL Serge2, LÉVESQUE Sébastien2

1Dynacare, Laval, QC.
2Sherbrooke Genomic Medicine, Sherbrooke, QC.

Pompe disease is a rare lysosomal storage disorder caused by recessive mutations in the GAA gene, for which enzymatic replacement therapy is available. Pompe disease can present with muscle weakness and elevated CK, and can mimic symptoms from many other neuromuscular disorders. Further complicating the diagnosis of Pompe disease, enzymatic levels can be reduced or borderline in carriers of a GAA mutation or in individuals who carry pseudodeficiency alleles, and access to genetic testing through traditional channels can be limited. Through case examples, we describe the success of a combined enzymatic and next-generation sequencing based testing program for identification of individuals affected with Pompe and other neuromuscular diseases. This program, a pilot project financially supported by Sanofi-Genzyme*, provides to genetic testing for patients with neuromuscular disease and is complimented by genetic counselling support to the ordering clinician. The diagnostic yield of this NGS panel has been estimated to 32% in a cohort of patients presenting with various muscle weakness patterns, and showing abnormal CK levels, myopathic EMG or abnormal (non-specific) muscle biopsy (Levesque et al. 2016. PMID: 26809617). In addition to diagnosing individuals affected with Pompe disease, this program permits the diagnosis of individuals with other rare muscular disorders, many of whom have been on a diagnostic odyssey their entire lives.

*Patient eligibility criteria need to be fulfilled to gain access to the program.


Friday October 12, 9:45 – 10:00

OF06 A familial investigation of recurrent Osteogenesis Imperfect over three decades

Claire BASCUNANA1, David ROSENBLATT1, Franck RAUCH1, Pierre MOFFATT1, Francis H. GLORIEUX1

1McGill Department of Human Genetics, Montréal, QC, Canada

Osteogenesis imperfecta (OI) is a spectrum of bone genetic condition with variable severity from mild phenotype to perinatal letality. Before the advances of genomic, diagnostic was made via imaging and clinical examination. Then, the biochemical analyses allowed further characterisation of its physiopathology using protein electrophoresis on collagen from fibroblasts. Today, OI is known to be genetically heterogeneous and is directly diagnosed by molecular sequencing with more than 20 different genes involved. Although its inheritance is known to be mainly autosomal dominant de novo, some OI forms of autosomal recessive inheritance has been described, and recurrent diagnoses of autosomal dominant OI has been reported as well through the mechanism of germline mosaicism since the 90’s.

We present a case of recurrence of a lethal form of OI in siblings where 3 successive pregnancies were affected, between 1977 and 1982. The first affected pregnancy was misdiagnosed as a phocomelia after neonatal death and autopsy, and low recurrence risk was given to the couple. The second pregnancy was properly diagnosed as affected with OI thanks to radiography imaging after the neonatal death. The third affected pregnancy displayed abnormal skeletal ultrasonographic findings and the couple took the decision to have termination of the pregnancy. At this time, autosomal recessive inheritance was mentioned to the couple, with a recurrence risk of 25% for further pregnancies. In 2017, a non-affected daughter of this couple is seen in Prenatal Genetics at the Jewish General Hospital for her first pregnancy for which she would like be reassured regarding the risk of OI. In the medical chart of her mother that we were able to get after signature of a release of information, we discovered a result of biochemical analysis from 1986 using parental fibroblast and a sample from amniocentesis performed on the last affected pregnancy, leaning toward an autosomal dominant form of the condition from the electrophoresis pattern obtained. Surprisingly, a sample of DNA from the last affected pregnancy was stored since 1982 at the Shriners Hospital for Children. We wanted to be able to identify the causal mutation of recurrence of OI in this family, in order to offer proper genetic counselling to our patient. The foetal sample from 1982, sent for a molecular panel of 22 genes known to be associated to OI, revealed the heterozygous pathogenic novel mutation COL1A1 (c.2336G>A). This result confirmed the diagnostic of OI in its dominant form, and validated the explanation of germline mosaicism as the more likely to have caused the familial recurrence.

Thanks to the rise of genomic technologies, and the storage of biological material for more than 30 years, we resolved the uncertainty of a mother with a delicate reproductive past while reassuring her daughter, whom the recurrence risk of OI for all her pregnancies would be similar to general population.