Whole genome sequencing in paediatric channelopathy and cardiomyopathy

PMID: 38586174 Gene: MYBPC3 HGNC ID: 7551

Case2: 12-year-old boy (Patient 2) DiseaseAssertion: DCM FamilyInfo: Family history unremarkable. ParentalTesting: The MYBPC3 variant was inherited from his father. The father’s cardiac phenotype is not reported. CasePresentingHPOs: HP:0001644, HP:0003546 CaseHPOFreeText: Severely depressed biventricular function; heart transplantation for decompensated heart failure. CaseNotHPOs: CaseNotHPOFreeText: CasePreviousTesting: Previous WES was negative; the variant’s intronic region was not adequately covered. Genotyping Method: Whole-genome sequencing (WGS; Illumina NovaSeq 6000; aligned to hg19/GRCh37). FunctionalAnalysis: SpliceAI predicted a potential splicing effect; no functional assay in this patient is reported. Variant: NM_000256.3:c.1224-80G>A (heterozygous intronic variant) ClinVar: 693982 CAID: CA221697326 gnomAD: 0.0000637 AdditionalInfo: The authors classified the variant as a VUS in this DCM case because evidence for a MYBPC3–DCM relationship is limited. ClinVar currently reports a pathogenic/likely pathogenic aggregate classification, primarily in relation to HCM. Reanalysis found no second MYBPC3 variant.

Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes

PMID: 31361967

Gene: MYBPC3

HGNC ID: 7551

Case1: 50 year old male DiseaseAssertion: HCM; hydroxychloroquine cardiotoxicity FamilyInfo: Six children undergoing predictive testing for the familial MYBPC3 variant; family history not reported ParentalTesting: CasePresentingHPOs: HP:0001639 CaseHPOFreeText: Monomorphic ventricular tachycardia, dyspnea, nausea, vomiting, biventricular hypertrophy, systolic dysfunction, cardiogenic shock CaseNotHPOs: CaseNotHPOFreeText: CasePreviousTesting: Prior CMR showed nonobstructive HCM; cardiomyopathy gene panel identified the variant Genotyping Method: Cardiomyopathy gene panel FunctionalAnalysis: Altered splicing with exon 30 skipping; authors describe a nonfunctional protein or premature stop codon Variant: c.3330+5G>C ClinVar: 42706 CAID: gnomAD: 0.03% (as reported in the article) AdditionalInfo: Long-term hydroxychloroquine exposure for malaria prophylaxis; biopsy findings were consistent with both HCM and hydroxychloroquine cardiotoxicity

Chronic Activation of Tubulin Tyrosination Improves Heart Function

PMID: 39279670 Gene: MYBPC3 HGNC ID: 7551