First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family.
J Hum Genet
; 61(4): 295-300, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26657938
ABSTRACT
Perrault syndrome (MIM #233400) is a rare autosomal recessive disorder characterized by ovarian dysgenesis and primary ovarian insufficiency in females, and progressive hearing loss in both genders. Recently, mutations in five genes (HSD17B4, HARS2, CLPP, LARS2 and C10ORF2) were found to be responsible for Perrault syndrome, although they do not account for all cases of this genetically heterogeneous condition. We used whole-exome sequencing to identify pathogenic variants responsible for Perrault syndrome in an Italian pedigree with two affected siblings. Both patients were compound heterozygous for two novel missense variants within the mitochondrial leucyl-tRNA synthetase (LARS2) NM_015340.3c.899C>T(p.Thr300Met) and c.1912G>A(p.Glu638Lys). Both variants cosegregated with the phenotype in the family. p.Thr300 and p.Glu638 are evolutionarily conserved residues, and are located, respectively, within the editing domain and immediately before the catalytically important KMSKS motif. Homology modeling using as template the E. coli leucyl-tRNA synthetase provided further insights on the possible pathogenic effects of the identified variants. This represents the first independent replication of the involvement of LARS2 mutations in Perrault syndrome, contributing valuable information for the further understanding of this disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Disgenesia Gonadal 46 XX
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Sequenciamento de Nucleotídeos em Larga Escala
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Aminoacil-tRNA Sintetases
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Perda Auditiva Neurossensorial
Limite:
Female
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Humans
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article