title: A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred.
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.
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Mory
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Ruiz
authors.affiliation: 1] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel [2] Department of Nursing, University of Haifa, Haifa, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Dagan
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Evgenia A
authors.initials: EA
authors.lastname: Yakovtseva
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Kurolap
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Parés
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Farrés
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000853:Anophthalmos / Q000201:enzymology / Q000235:genetics*; D018912:Arabs; D005260:Female; D006720:Homozygote; D006801:Humans; D007557:Israel; D008297:Male; D008850:Microphthalmos / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)