Congenica platform provides variant review and assessment to support conclusive diagnoses
for patients with complex and commonly misdiagnosed bleeding disorders in a
large multicenter genomic study.
MYH9-related disorder (MYH9-RD) is a complex condition that can have many signs and
symptoms, including bleeding problems, hearing loss, kidney disease, and cataracts.
The complexity and variability of patients’ clinical presentation can make the diagnosis of
MYH9-RD extremely challenging, even by skilled clinicians at specialist centers. As a consequence, a significant number of patients with MYH9-RD are initially misdiagnosed and can receive ineffective and potentially harmful treatments.
A recent study by an international collaboration of researchers has performed the first systematic analysis of MYH9 variants using high throughput sequencing (HTS) analysis in a large cohort of patients and controls enrolled from over 100 centers worldwide.
Encouragingly the results demonstrate that an HTS-based strategy is a reliable method to
reach a conclusive diagnosis of MYH9-RD in clinical practice.
This study collected samples and phenotypic data in more than 3,000 patients with a
bleeding or platelet disorder, and sequenced them using HTS.
Genetic variants were assessed using the Congenica® clinical decision support platform to visualize the data, assign variant pathogenicity and contribution to phenotype based on the clinical picture, predict consequence in the protein, and check the presence of variants in the Human Gene Mutation Database (HGMD (Stenson, et al 2017)) and their allele frequency in control datasets such as the genome Aggregation Database (gnomAD) (Lek, et al 2016)).
Following this analysis, a total of 23 patients were conclusively diagnosed with MYH9-RD
after the discovery and characterization of pathogenic and likely pathogenic variants in the MYH9 gene.
Eleven of these patients had a previous clinical suspicion of MYH9-RD, while 12 cases were
coded as having an “unclassified platelet disorder” before being analyzed with Congenica.
In conclusion, the study was successful in detecting variants causing MYH9-RD, highlighting the heterogeneity of the clinical presentation of the disorder, and expanding the knowledge of the range of MYH9 genotype-phenotype associations.
The application of HTS-based strategies is revealed to be a reliable and fast method to reach a conclusive diagnosis of MYH9-RD allowing clinicians to predict the course of extra-hematological symptoms and may consequently guide the implementation of personalized clinical monitoring and therapies.
Find out how Congenica can support you in the diagnosis of complex disorders by booking a personalized demo with a member of the team.
See how Congenica can maximize the efficiency of your NGS data analysis and increase your diagnostic yield and confidence.