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

Cold Spring Harbor Molecular Case Studies
Catherine Kiraly-BorriSaquib A Lakhani

Abstract

Variants in the mitochondrial alanyl-tRNA synthetase 2 gene AARS2 (OMIM 612035) are associated with infantile mitochondrial cardiomyopathy or later-onset leukoencephalopathy 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.Cys218Leufs*6) 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.

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Citations

May 18, 2019·American Journal of Medical Genetics. Part a·Siddharth SrivastavaSakkuBai Naidu
Aug 9, 2019·Endocrinology·Dov TiosanoDavid A Buchner
May 1, 2021·International Journal of Molecular Sciences·Sonia FigucciaPaola Goffrini
Sep 30, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Nobuhiko OkamotoKenjiro Kosaki

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Datasets Mentioned

BETA
SCV000882690

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BETA
cesarean section
X
ray
aminoacylation

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GATK
ANNOVAR

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