Exome sequencing reveals pathogenic mutations in the LARS2 and HSD17B4 genes associated with Perrault syndrome and D-bifunctional protein deficiency in Moroccan families.
Mol Biol Rep
; 51(1): 850, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-39052101
ABSTRACT
BACKGROUND:
Syndromic hearing loss (SHL) is characterized by hearing impairment accompanied by other clinical manifestations, reaching over 400 syndromes. Early and accurate diagnosis is essential to understand the progression of hearing loss and associated systemic complications. METHODS ANDRESULTS:
In this study, we investigated the genetic etiology of sensorineural hearing loss in three Moroccan patients using whole exome sequencing (WES). The results revealed in two families Perrault syndrome caused by LARS2, p. Asn153His; p. Thr629Met compound heterozygous variants in two siblings in one family; and p. Thr522Asn, a homozygous variant in two sisters in another. The patient in the third family was diagnosed with D-bifunctional protein deficiency (D-BPD), linked to compound heterozygous mutations p. Asn457Tyr and p. Val643Argfs*5 in HSD17B4. Molecular dynamic simulation results showed that Val643Argfs*5 does not prevent HSD17B4 protein from binding to the PEX5 receptor, but further studies are recommended to verify its effect on HSD17B4 protein functionality.CONCLUSION:
These results highlight the effectiveness of WES in identifying pathogenic mutations involved in heterogeneous disorders and the usefulness of bioinformatics in predicting their effects on protein structure.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Disgenesia Gonadal 46 XX
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Proteína Multifuncional do Peroxissomo-2
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Aminoacil-tRNA Sintetases
/
Perda Auditiva Neurossensorial
Limite:
Child
/
Female
/
Humans
/
Male
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article