ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features

Cold Spring Harb Mol Case Stud. 2017 Sep 1;3(5):a001859. doi: 10.1101/mcs.a001859.

Ahmet Okay Çağlayan ¹ ², Rabia Gonul Sezer ³, Hande Kaymakçalan ⁴, Ege Ulgen ², Taner Yavuz ⁵, Jacob F Baranoski ², Abdulkadir Bozaykut ³, Akdes Serin Harmanci ², Yalim Yalcin ⁶, Mark W Youngblood ², Katsuhito Yasuno ², Kaya Bilgüvar ⁷, Murat Gunel ²

Affiliations

1 Department of Medical Genetics, School of Medicine, Istanbul Bilim University, Istanbul 34394, Turkey.
2 Departments of Neurosurgery, Neurobiology and Genetics, Yale School of Medicine, New Haven, Connecticut 06510, USA.
3 Department of Pediatrics, University of Health Sciences, Zeynep Kamil Maternity and Childrens' Diseases Training and Research Hospital, Istanbul 34668, Turkey.
4 Department of Pediatrics, School of Medicine, Istanbul Bilim University, Istanbul 34394, Turkey.
5 Division of Pediatric Cardiology, Department of Pediatrics, Zeynep Kamil Maternity and Childrens' Diseases Training and Research Hospital, Istanbul 34668, Turkey.
6 Division of Pediatric Cardiology, Department of Pediatrics, School of Medicine, Istanbul Bilim University, Istanbul 34394, Turkey.
7 Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut 06510, USA.

PMID: 28630369 DOI: 10.1101/mcs.a001859

Abstract

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 as a high-throughput discovery tool for identifying novel disease-causing genes. We describe a male infant with primary dilated cardiomyopathy who was diagnosed using intrauterine echocardiography and found to progress to hypertrophic cardiomyopathy after birth. This proband was born to a nonconsanguineous family with a past history of a male fetus that died because of cardiac abnormalities at 30 wk 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.

Keywords

hypertrophic cardiomyopathy.

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