Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin

Zeinab Ravesh, Mohammed E. El Asrag, Nicole Weisschuh, Martin McKibbin, Peggy Reuter, Christopher M. Watson, Britta Baumann, James A. Poulter, Sundus Sajid, Evangelia S. Panagiotou, James O'Sullivan, Zakia Abdelhamed, Michael Bonin, Mehdi Soltanifar, Graeme C. M. Black, Muhammad Amin-ud Din, Carmel Toomes, Muhammad Ansar, Chris F. Inglehearn, Bernd WissingerManir Ali

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members.

METHODS: Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects.

RESULTS: In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244-2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin.

CONCLUSIONS: In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa.

Original languageEnglish
Pages (from-to)236-43
Number of pages8
JournalMolecular Vision
Volume21
Publication statusPublished - 7 Mar 2015

Keywords

  • Adolescent
  • Adult
  • Child
  • Consanguinity
  • DNA Mutational Analysis
  • Exons
  • Female
  • Genes, Recessive
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pakistan
  • Proteins/genetics
  • RNA Splicing
  • Retinitis Pigmentosa/genetics

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