Case1: Male, Infant,

DiseaseAssertion: Dilated cardiomyopathy

FamilyInfo: Healthy, reportedly non-consanguineous, and had no known history of cardiomyopathy, heart failure, arrhythmia, sudden unexplained death, neuromuscular disease, or inherited metabolic disorder

ParentalTesting: Both parents were confirmed as heterozygous carriers by trio-based whole-exome sequencing.

CasePresentingHPOs: HP:0012378, HP:0030831, HP:0030864, HP:0033113, HP:0001712,

CaseHPOFreeText: “On arrival, he appeared pale, tachypneic, and fatigued, with subcostal retractions and scattered rhonchi and crepitations on chest auscultation. Cardiac examination revealed a gallop rhythm. Electrocardiography demonstrated biatrial enlargement, left ventricular hypertrophy, and borderline QT prolongation.”

CaseNotHPOs: NR

CaseNotHPOFreeText: No dysmorphic features recognized clinically, normal social interaction and visual tracking for age, normal brain MRI (normal cerebral structure and myelination, no malformation or demyelination), normal skeletal survey, creatine kinase within normal range, broad metabolic screening unrevealing, no pericardial effusion on echocardiography, no overt skeletal myopathy clinically recognized, negative SMA molecular testing, negative Prader–Willi syndrome methylation analysis

CasePreviousTesting: Broad metabolic screening was unrevealing. Creatine kinase was within the normal range. Molecular testing for spinal muscular atrophy and methylation analysis for Prader–Willi syndrome was negative. Brain magnetic resonance imaging performed at 9 months of age demonstrated normal cerebral structure and myelination, without malformation or evidence of demyelination. A skeletal survey was also normal. Additional investigations for muscular dystrophy and primary myopathic disorders had been initiated but were still incomplete at the time of his acute deterioration.

Genotyping Method: Trio-based whole-exome sequencing. Genomic DNA extracted from peripheral blood. Exome enrichment targeting coding exons and flanking splice junctions of >20,000 protein-coding genes. Illumina platform, mean on-target coverage >100×, ≥98% of targeted bases covered at ≥20× depth. Alignment to GRCh37/hg19, GATK-based variant calling pipeline.

FunctionalAnalysis: No functional analysis was performed.

Variant: NM_000432.4:c.413T>A

ClinVar: 840366

CAID: CA042802

gnomAD: 12:111348969 A / T, chr12-110911165-A-T