Case1: 7-year-old girl

DiseaseAssertion: HCM

FamilyInfo: clinical history was negative. Unable to obtain clinical information on first-degree relatives. Both parents carried MYH7 mutation.

CasePresentingHPOs: HP:0025490, HP:0100598

"Myocardial bridging, Pulmonary edema"

CaseHPOFreeText: In the last weeks, patient had frequently been visited by a pediatrician to treat seasonal allergies. Full-body CT-scan was performed to exclude abuse or trauma and did not show any anomaly. The heart (weight: 240 g, longitudinal diameter: 11 cm, transverse diameter: 10 cm, thickness of the anterior wall of the right ventricle: 0·3 cm, thickness of the left ventricle: 1·0 cm) did not reveal morphologic or structural anomalies of ventricular walls and valves. The coronary circulation was right-dominant and presented myocardial bridging (length: 1·1 cm, thickness: 0·5 cm) involving the middle segment of the left anterior descending coronary artery. No other significant elements were found upon macroscopic observation, with the exception of pulmonary edema. Histopathological examination showed patchy interstitial fibrosis, myocyte disarray and waving of the myofibers in the tissue surrounding the tunneled artery. Several areas of interstitial and subendocardic fibrosis in the other samples of the left ventricular myocardium were also observed.

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: The low value of serum tryptase (6·12 µg/L) excluded a fatal anaphylaxis. Toxicology tests were negative. NGS analysis used a custom resequencing panel which included 147 genes associated with cardiomyopathies and channelopathies. Authors identified five rare genetic variants in heterozygous state (Table 4).

GenotypingMethod: Genomic DNA was extracted from postmortem whole blood of the proband. Whole blood samples of the proband mother, father and sister were obtained to extract genomic DNA and thus to perform Sanger sequencing to analyze the segregation of each genetic variant identified by NGS. Authors performed Sanger sequencing on the DNA extracted from the mother, the father and the sister of the proband. The father carried both variants identified in the DPP6 gene, whereas the mother carried the rare variants identified in MYH7, SCN2B and NOTCH1. The sister carried all the genetic variants.

Variant: NM_000257.4:c.2585C>T

ClinVar: 36636

CAID: CA012680

gnomAD: https://gnomad.broadinstitute.org/variant/14-23894072-G-A

0.00008014 African/African-American