Loss-of-Function CARS1 Variants in a Patient With Microcephaly, Developmental Delay, and a Brittle Hair Phenotype

被引：0

作者：

Del Greco, Christina ^{[1
]}

Kuo, Molly E. ^{[1
,2
,3
]}

Smith, Desiree E. C. ^{[4
]}

Mendes, Marisa I. ^{[4
]}

Salamons, Gajja S. ^{[4
]}

Nemcovic, Marek ^{[5
]}

Kodrikova, Rebeka ^{[5
]}

Sestak, Sergej ^{[5
]}

Stancheva, Malina ^{[6
]}

Antonellis, Anthony ^{[1
,2
,7
]}

机构：

[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Med Sch, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Med Sch, Med Scientist Training Program, Ann Arbor, MI USA

[4] Univ Amsterdam, Amsterdam UMC, Lab Genet Metab Dis, Amsterdam, Netherlands

[5] Slovak Acad Sci, Inst Chem, Dept Glycobiol, Bratislava, Slovakia

[6] Med Dent Ctr Mediva, Sofia, Bulgaria

[7] Univ Michigan, Med Sch, Dept Neurol, Ann Arbor, MI 48109 USA

来源：

MOLECULAR GENETICS & GENOMIC MEDICINE | 2025年 / 13卷 / 02期

关键词：

MUTATIONS;

D O I：

10.1002/mgg3.70078

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

BackgroundMutations in cysteinyl-tRNA synthetase (CARS1) have been implicated in a multisystem disease including microcephaly, developmental delay, and brittle hair and nail phenotypes.MethodsHere, we present a patient with hepatopathy, hypothyroidism, short stature, developmental delay, microcephaly, muscular hypotonia, brittle hair, and ataxia. The patient underwent exome sequencing to identify potentially pathogenic genetic variants. In addition, identified variants were assessed using yeast complementation assays to determine functional consequences.ResultsExome sequencing determined that the patient is compound heterozygous for p.Arg341His and p.Arg370Trp CARS1. Yeast complementation assays showed that the p.Arg341His variant has a hypomorphic effect and that the p.Arg370Trp variant causes a complete loss-of-function effect.ConclusionThis study is the second report of pathogenic CARS1 variants and expands the allelic and phenotypic heterogeneity of CARS1-associated disease.

引用

页数：6

共 21 条

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