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Your search keyword '"Otx Transcription Factors chemistry"' showing total 2 results
Start Over Descriptor "Otx Transcription Factors chemistry" Topic retinal dystrophies
2 results on '"Otx Transcription Factors chemistry"'

1. Homozygous variant in OTX2 and possible genetic modifiers identified in a patient with combined pituitary hormone deficiency, ocular involvement, myopathy, ataxia, and mitochondrial impairment.

Author

Catania A, Legati A, Peverelli L, Nanetti L, Marchet S, Zanetti N, Lamperti C, and Ghezzi D

Subjects
Adult, Aged, Alleles, Amino Acid Sequence, Amino Acid Substitution, Ataxia diagnosis, DNA, Mitochondrial, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Hypopituitarism diagnosis, Karyotyping, Male, Mitochondria metabolism, Muscular Diseases diagnosis, Otx Transcription Factors chemistry, Pedigree, Phenotype, Retinal Dystrophies diagnosis, Ataxia genetics, Homozygote, Hypopituitarism genetics, Mitochondria genetics, Muscular Diseases genetics, Mutation, Otx Transcription Factors genetics, Retinal Dystrophies genetics
Abstract

Here we report on a singleton patient affected by a complicated congenital syndrome characterized by growth delay, retinal dystrophy, sensorineural deafness, myopathy, ataxia, combined pituitary hormone deficiency, associated with mitochondrial impairment. Targeted clinical exome sequencing led to the identification of a homozygous missense variant in OTX2. Since only dominant mutations within OTX2 have been associated with cases of syndromic microphthalmia, retinal dystrophy with or without pituitary dysfunctions, this represents the first report of an OTX2 recessive mutation. Part of the phenotype, including ataxia, myopathy and multiple mitochondrial respiratory chain defects, seemed not related to OTX2. Further analysis of next generation sequencing (NGS) data revealed additional candidate variants: a homozygous variant in LETM1, and heterozygous rare variants in AFG3L2 and POLG. All three genes encode mitochondrial proteins and the last two are known to be associated with ataxia, a neurological sign present also in the father of the proband. With our study, we aim to encourage the integration of NGS data with a detailed analysis of clinical description and family history in order to unravel composite genotypes sometimes associated with complicated phenotypes., (© 2019 Wiley Periodicals, Inc.)

Published
2019
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2. OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium.

Author

Vincent A, Forster N, Maynes JT, Paton TA, Billingsley G, Roslin NM, Ali A, Sutherland J, Wright T, Westall CA, Paterson AD, Marshall CR, and Héon E

Subjects
Adolescent, Adult, Amino Acid Sequence, Child, Child, Preschool, Computational Biology, DNA Mutational Analysis, Exome, Female, Genetic Linkage, Genotype, Humans, Male, Microsatellite Repeats, Middle Aged, Models, Molecular, Molecular Sequence Data, Otx Transcription Factors chemistry, Pedigree, Polymorphism, Single Nucleotide, Protein Conformation, Retinal Dystrophies diagnosis, Sequence Alignment, Vision Tests, Young Adult, Genes, Dominant, Mutation, Otx Transcription Factors genetics, Retinal Dystrophies genetics, Retinal Dystrophies pathology, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology
Abstract

Purpose: To identify the genetic cause of autosomal-dominant pattern dystrophy (PD) of the retinal pigment epithelium (RPE) in two families., Methods and Results: Two families with autosomal-dominant PD were identified. Eight members of family 1 (five affected) were subjected to whole-genome SNP genotyping; multipoint genome-wide linkage analysis identified 7 regions of potential linkage, and genotyping four additional individuals from family 1 resulted in a maximum logarithm of odds score of 2.09 observed across four chromosomal regions. Exome sequencing of two affected family 1 members identified 15 shared non-synonymous rare coding sequence variants within the linked regions; candidate genes were prioritised and further analysed. Sanger sequencing confirmed a novel heterozygous missense variant (E79K) in orthodenticle homeobox 2 (OTX2) that segregated with the disease phenotype. Family 2 with PD (two affected) harboured the same missense variant in OTX2. A shared haplotype of 19.68 cM encompassing OTX2 was identified between affected individuals in the two families. Within the two families, all except one affected demonstrated distinct 'patterns' at the macula. In vivo structural retinal imaging showed discrete areas of RPE-photoreceptor separation at the macula in all cases. Electroretinogram testing showed generalised photoreceptor degeneration in three cases. Mild developmental anomalies were observed, including optic nerve head dysplasia (four cases), microcornea (one case) and Rathke's cleft cyst (one case); pituitary hormone levels were normal., Conclusions: This is the first report implicating OTX2 to underlie PD. The retinal disease resembles conditional mice models that show slow photoreceptor degeneration secondary to loss of Otx2 function in the adult RPE., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Published
2014
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