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

doi:10.1038/ejhg.2013.157

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

Department of Nursing

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	419-422
Number of pages	4
Journal	European Journal of Human Genetics
Volume	22
Issue number	3
DOIs	https://doi.org/10.1038/ejhg.2013.157
State	Published - 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
Genetics(clinical)

Access to Document

10.1038/ejhg.2013.157

Cite this

@article{3ad97e062f6d478ba1aff599349b379b,

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.",

keywords = "ALDH1A3 gene, anophthalmia/microphthalmia, homozogosity mapping",

author = "Adi Mory and Ruiz, {Francesc X.} and Efrat Dagan and Yakovtseva, {Evgenia A.} and Alina Kurolap and Xavier Par{\'e}s and Jaume Farr{\'e}s and Ruth Gershoni-Baruch",

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 Econom{\'i}a y Competitividad (BFU2011-24176) and Generalitat de Catalunya (2009 SGR 795).",

year = "2014",

month = mar,

doi = "10.1038/ejhg.2013.157",

language = "English",

volume = "22",

pages = "419--422",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Springer Nature",

number = "3",

}

TY - JOUR

T1 - A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred

AU - Mory, Adi

AU - Ruiz, Francesc X.

AU - Dagan, Efrat

AU - Yakovtseva, Evgenia A.

AU - Kurolap, Alina

AU - Parés, Xavier

AU - Farrés, Jaume

AU - Gershoni-Baruch, Ruth

N1 - 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).

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - ALDH1A3 gene

KW - anophthalmia/microphthalmia

KW - homozogosity mapping

UR - http://www.scopus.com/inward/record.url?scp=84894309585&partnerID=8YFLogxK

U2 - 10.1038/ejhg.2013.157

DO - 10.1038/ejhg.2013.157

M3 - Article

C2 - 23881059

AN - SCOPUS:84894309585

SN - 1018-4813

VL - 22

SP - 419

EP - 422

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this