ALPK3 GENE MUTATION IN A PATIENT WITH CONGENITAL CARDIOMYOPATHY AND DYSMORPHIC FEATURES.
Cold Spring Harb Mol Case Stud. 2017 Jun 19;:
Authors: Cağlayan AO, Sezer RG, Kaymakcalan H, Ulgen E, Yavuz T, Baranoski JF, Bozaykut A, Serin Harmanci A, Yalcin Y, Youngblood MW, Yasuno K, Bilguvar K, Gunel M
Primary cardiomyopathy is one of the most common inherited cardiac diseases and harbors significant phenotypic and genetic heterogeneity. Because of this, genetic testing has become standard in treatment of this disease group. Indeed, in recent years, next-generation DNA sequencing has found broad applications in medicine, both as a routine diagnostic tool for genetic disorders and also as a high-throughput discovery tool for identifying novel disease causing genes. We describe a male infant with primary dilated cardiomyopathy that was diagnosed using intrauterine echocardiography, and found to progress to hypertrophic cardiomyopathy after birth. This proband was born to a non-consanguineous family with a past history of a male fetus that died due to cardiac abnormalities at 30 weeks of gestation. Using whole-exome sequencing, a novel homozygous frameshift mutation (c.2018delC; p.Gln675SerfsX30) in ALPK3 was identified and confirmed with Sanger sequencing. Heterozygous family members were normal with echocardiographic examination. To date, only two studies have reported homozygous pathogenic variants of ALPK3, with a total of seven affected individuals with cardiomyopathy from four unrelated consanguineous families. We include a discussion of the patient’s phenotypic features and a review of relevant literature findings.
PMID: 28630369 [PubMed – as supplied by publisher]