Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/7827
Title: Novel splice-site and missense mutations in the ALDH1A3 gene underlying autosomal recessive anophthalmia/microphthalmia
Authors: Semerci, C.N.
Kalay, E.
Yıldırım, Cem
Dinçer, T.
Ölmez, A.
Toraman, B.
Koçyigit, Ali
Keywords: adolescent
ALDH1A3 gene
amino acid substitution
anophthalmia
article
autism
chromosome 15q
clinical article
controlled study
exon skipping
female
gene
gene locus
gene mapping
genetic association
genotype
human
human cell
male
mental deficiency
microphthalmia
missense mutation
mutational analysis
pedigree analysis
priority journal
reverse transcription polymerase chain reaction
RNA splicing
sequence analysis
single nucleotide polymorphism
Adolescent
Aldehyde Oxidoreductases
Anophthalmos
Base Sequence
Child
Chromosomes, Human, Pair 15
DNA Mutational Analysis
Female
Genes, Recessive
Genotype
Humans
Male
Microphthalmos
Molecular Sequence Data
Mutation, Missense
Pedigree
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Reverse Transcriptase Polymerase Chain Reaction
RNA Splice Sites
Publisher: BMJ Publishing Group
Abstract: Aim: This study aimed to identify the underlying genetic defect responsible for anophthalmia/microphthalmia. Methods: In total, two Turkish families with a total of nine affected individuals were included in the study. Affymetrix 250 K single nucleotide polymorphism genotyping and homozygosity mapping were used to identify the localisation of the genetic defect in question. Coding region of the ALDH1A3 gene was screened via direct sequencing. cDNA samples were generated from primary fibroblast cell cultures for expression analysis. Reverse transcriptase PCR (RT-PCR) analysis was performed using direct sequencing of the obtained fragments. Results: The causative genetic defect was mapped to chromosome 15q26.3. A homozygous G>A substitution (c.666G>A) at the last nucleotide of exon 6 in the ALDH1A3 gene was identified in the first family. Further cDNA sequencing of ALDH1A3 showed that the c.666G>A mutation caused skipping of exon 6, which predicted in-frame loss of 43 amino acids (p. Trp180-Glu222del). A novel missense c.1398C>A mutation in exon 12 of ALDH1A3 that causes the substitution of a conserved asparagine by lysine at amino acid position 466 (p.Asn466Lys) was observed in the second family. No extraocular findings - except for nevus flammeus in one affected individual and a variant of Dandy-Walker malformation in another affected individual - were observed. Autistic-like behaviour and mental retardation were observed in three cases. Conclusions: In conclusion, novel ALDH1A3 mutations identified in the present study confirm the pivotal role of ALDH1A3 in human eye development. Autistic features, previously reported as an associated finding, were considered to be the result of social deprivation and inadequate parenting during early infancy in the presented families.
URI: https://hdl.handle.net/11499/7827
https://doi.org/10.1136/bjophthalmol-2013-304058
ISSN: 0007-1161
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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