Dataset Information

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

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.

SUBMITTER: Caglayan AO

PROVIDER: S-EPMC5593152 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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<i>ALPK3</i> gene mutation in a patient with congenital cardiomyopathy and dysmorphic features.

Çağlayan Ahmet Okay AO Sezer Rabia Gonul RG Kaymakçalan Hande H Ulgen Ege E Yavuz Taner T Baranoski Jacob F JF Bozaykut Abdulkadir A Harmanci Akdes Serin AS Yalcin Yalim Y Youngblood Mark W MW Yasuno Katsuhito K Bilgüvar Kaya K Gunel Murat M

Cold Spring Harbor molecular case studies 20170901 5

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 pri ...[more]

PMID: 28630369

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Project description:Congenital thrombotic thrombocytopenic purpura (TTP) is a rare hereditary disease with a high mortality rate; however, improved patient survival is possible with prompt diagnosis and treatment. The clinical features and mutation sites of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) in congenital TTP were analyzed in a neonate with suspected congenital TTP. High-throughput sequencing, polymerase chain reaction, and Sanger sequencing were utilized for screening of genes related to thrombocytopenic diseases and ADAMTS13 gene mutation testing on blood samples from the neonate and the parents. Domestic and foreign literature reporting the clinical features and variants of ADAMTS13 in neonates with congenital TTP were retrieved, compared, and analyzed. The patient in this case was a girl who had been born for 1 h and admitted to the hospital due to "dyspnea for 1 h." Routine blood tests on admission revealed profound thrombocytopenia. She quickly developed symptoms of systemic hemorrhage and eventually died. The neonate had two older sisters who had died of idiopathic thrombocytopenia and hemorrhage within 24 h of birth. Genetic testing showed that the neonate harbored a compound heterozygous mutation in ADAMTS13, c.1187G>A/c.1595G>T, which is a novel variant. Of the 12 cases (1 case in China and 11 cases in other countries) of congenital TTP in neonates that have been reported globally, ADAMTS13 mutation analysis was only performed in eight neonates. Common clinical manifestations included dyspnea of unknown etiology, bruising, jaundice, hemorrhage, and thrombocytopenia. Hence, the current case contributes to our understanding of the clinical manifestations and types of variants in neonates with congenital TTP. Our results demonstrate the efficacy of high-throughput sequencing technology in genetic testing of neonates suspected with congenital TTP and have revealed a novel compound missense mutation in ADAMTS13 that has not been reported in China or elsewhere.

Dataset Information

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

Publications

<i>ALPK3</i> gene mutation in a patient with congenital cardiomyopathy and dysmorphic features.

Similar Datasets

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