Siblings with lethal primary pulmonary hypoplasia and compound heterozygous variants in the AARS2 gene: Further delineation of the phenotypic spectrum

Catherine Kiraly-Borri, Gareth Jevon, Weizhen Ji, Lauren Jeffries, Jamie Lee Ricciardi, Monica Konstantino, Kate G. Ackerman, Saquib A. Lakhani

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Variants in the mitochondrial alanyl-tRNA synthetase 2 gene AARS2 (OMIM 612035) are associated with infantile mitochondrial cardiomyopathy or later-onset leukoen-cephalopathy with premature ovarian insufficiency. Here, we report two newborn siblings who died soon after birth with primary pulmonary hypoplasia without evidence of cardiomyopathy. Whole-exome sequencing detected the same compound heterozygous AARS2 variants in both siblings (c.1774C>T, p.Arg592Trp and c.647dup, p.Cys218Leufs6) that have previously been associated with infantile mitochondrial cardiomyopathy. Segregation analysis in the family confirmed carrier status of the parents and an unaffected sibling. To our knowledge, this is the first report of primary pulmonary hypoplasia in the absence of cardiomyopathy associated with recessive AARS2 variants and further defines the phenotypic spectrum associated with this gene.

Original languageEnglish
Article numbera003699
JournalCold Spring Harbor Molecular Case Studies
Volume5
Issue number3
DOIs
Publication statusPublished - 1 Jan 2019

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