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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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