A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred

Adi Mory, Francesc X. Ruiz, Efrat Dagan, Evgenia A. Yakovtseva, Alina Kurolap, Xavier Parés, Jaume Farrés, Ruth Gershoni-Baruch

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14 Citations (Scopus)

Abstract

Nine affected individuals with isolated anophthalmia/microphthalmia from a large Muslim-inbred kindred were investigated. Assuming autosomal-recessive mode of inheritance, whole-genome linkage analysis, on DNA samples from four affected individuals, was undertaken. Homozygosity mapping techniques were employed and a 1.5-Mbp region, homozygous in all affected individuals, was delineated. The region contained nine genes, one of which, aldehyde dehydrogenase 1 (ALDH1A3), was a clear candidate. This gene seems to encode a key enzyme in the formation of a retinoic-acid gradient along the dorsoventral axis during an early eye development and the development of the olfactory system. Sanger sequence analysis revealed a missense mutation, causing a substitution of valine (Val) to methionine (Met) at position 71. Analyzing the p.Val71Met missense mutation using standard open access software (MutationTaster online, PolyPhen, SIFT/PROVEAN) predicts this variant to be damaging. Enzymatic activity, studied in vitro, showed no changes between the mutated and the wild-type ALDH1A3 protein. © 2014 Macmillan Publishers Limited.
Original languageEnglish
Pages (from-to)419-422
JournalEuropean Journal of Human Genetics
Volume22
Issue number3
DOIs
Publication statusPublished - 1 Mar 2014

Keywords

  • ALDH1A3 gene
  • anophthalmia/microphthalmia
  • homozogosity mapping

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