Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3

Saleem Ahmed, Musharraf Jelani, Nuha Alrayes, Hussein Sheikh Ali Mohamoud, Mona Mohammad Almramhi, Wasim Anshasi, Naushad Ali Basheer Ahmed, Jun Wang, Jamal Nasir, Jumana Yousuf Al-Aama

Research output: Contribution to JournalArticlepeer-review

Abstract

Perrault syndrome (PRLTS) is a clinically and genetically heterogeneous disorder. Both male and female patients suffer from sensory neuronal hearing loss in early childhood, and female patients are characterized by premature ovarian failure and infertility after puberty. Clinical diagnosis may not be possible in early life, because key features of PRLTS, for example infertility and premature ovarian failure, do not appear before puberty. Limb spasticity, muscle weakness, and intellectual disability have also been observed in PRLTS patients. Mutations in five genes, HSD17B4, HARS2, CLPP, LARS2, and C10orf2, have been reported in five subtypes of PRLTS. We discovered a consanguineous Saudi family with the PRLTS3 phenotype showing an autosomal recessive mode of inheritance. The patients had developed profound hearing loss, brain atrophy, and lower limb spasticity in early childhood. For molecular diagnosis, we complimented genome-wide homozygosity mapping with whole exome sequencing analyses and identified a novel homozygous mutation in exon 6 of CLPP at chromosome 19p13.3. To our knowledge, early onset with regression is a unique feature of these PRLTS patients that has not been reported so far. This study broadens the clinical spectrum of PRLTS3.
Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalJournal of the Neurological Sciences
Volume353
Issue number1-2
DOIs
Publication statusPublished - 15 Jun 2015

Keywords

  • Brain atrophy
  • CLPP
  • Novel homozygous mutation
  • Perrault syndrome type 3
  • Saudi Arabia
  • Whole-exome sequencing

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