부산대학교 도서관

• Expanding the phenotype of DNMT3A associated with Tatton-Brown Syndrome (TBRS) to cause a congenital myopathy. • DNMT3A is associated with episodes of rhabdomyolysis and myalgias. • DNA methylation profile matching other haploinsufficient TBRS cases, consistent with the loss of methyltransferase activity, provides functional evidence for variant pathogenicity. Pathogenic variants in DNMT3A are most commonly associated with Tatton-Brown-Rahman Syndrome (TBRS), but includes other phenotypes such as Heyn-Sproul-Jackson syndrome and acute myeloid leukemia (AML). We describe a patient presenting to the neuromuscular clinic with a de novo missense variant in DNMT3A where the striking clinical feature is that of a congenital myopathy with associated episodes of rhabdomyolysis, severe myalgias and chest pain along with phenotypic features associated with TBRS. Muscle biopsy showed minor myopathic features and cardiac investigations revealed mildly impaired bi-ventricular systolic function. We confirmed the DNA methylation profile matched haplo-insufficient TBRS cases, consistent with a loss of methyltransferase activity. Our report emphasizes the phenotypic overlap of patients with syndromic disorders presenting to neuromuscular clinics and limitations of gene panels in establishing a molecular diagnosis. [ABSTRACT FROM AUTHOR]