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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)419-422
Number of pages4
JournalEuropean Journal of Human Genetics
Volume22
Issue number3
DOIs
StatePublished - Mar 2014

Bibliographical note

Funding Information:
We are grateful to all family members for their participation in this study. We thank Gregg Duester who provided the ALDH1A3 cDNA clone. Affymetrix GeneChip Human Mapping 250K Nsp microarray was carried out in the Biological Services Unit at the Weizmann Institute. This work was supported in part by the Spanish Ministerio de Economía y Competitividad (BFU2011-24176) and Generalitat de Catalunya (2009 SGR 795).

Keywords

  • ALDH1A3 gene
  • anophthalmia/microphthalmia
  • homozogosity mapping

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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