LARS2-Perrault syndrome: a new case report and literature review

BMC Med Genet. 2020 May 18;21(1):109. doi: 10.1186/s12881-020-01028-8.

Abstract

Background: Perrault syndrome is a rare recessive and genetically heterogeneous disorder characterized by sensorineural hearing loss in males and females and gonadal dysgenesis in females. Mutations in seven different genes have been identified: HARS2, HSD17B4, CLLP, C10orf, ERAL1, TWNK and LARS2. To date, 19 variants have been reported in 18 individuals with LARS2-Perrault syndrome.

Case presentation: Here we describe the case of an 8-year-old girl with compound heterozygous missense mutations in the LARS2 gene. We identified two missense mutations [c.457A > C, p.(Asn153His) and c.1565C > A, p.(Thr522Asn)] and subsequent familial segregation showed that each parent had transmitted a mutation.

Conclusions: These results have implications for genetic counseling and provide insight into the functional role of LARS2. This case highlights the importance of an early diagnosis. Systematic genetic screening of children with hearing loss allows the early identification of a Perrault syndrome in order to ensure specific endocrinological surveillance and management to prevent secondary complications. Clinical data are compared with the other cases reported in the literature.

Keywords: LARS2; Perrault syndrome; Sensorineural hearing loss; Whole-exome sequencing.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Amino Acyl-tRNA Synthetases / genetics*
  • Biomarkers
  • Child
  • Disease Management
  • Female
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genotype
  • Gonadal Dysgenesis, 46,XX / diagnosis*
  • Gonadal Dysgenesis, 46,XX / genetics*
  • Gonadal Dysgenesis, 46,XX / therapy
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / therapy
  • Humans
  • Mutation*
  • Phenotype

Substances

  • Biomarkers
  • Amino Acyl-tRNA Synthetases
  • LARS2 protein, human

Supplementary concepts

  • Gonadal dysgenesis XX type deafness