Dataset Information

Temporal macular thinning associated with X-linked Alport syndrome.

ABSTRACT: Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS).To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype.Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain OCT and fundus photography. Temporal macular thinning was calculated from OCT measurements by comparing the ratio of the retinal thickness of the temporal to the nasal subfields with a published normative database.University departments of ophthalmology and nephrology.Thirty-two patients from 24 families.Temporal thinning index calculated from spectral domain OCT scans.All study patients had a mutation associated with the X-linked COL4A5 gene. Eleven different mutations were identified. Eleven of 32 patients (34%) expressed the L1649R mutation. Of a total of 63 eyes with available OCT scans, 44 (70%) had severe pathological temporal macular thinning. The L1649R mutation was associated with the least amount of severe temporal macular thinning and later onset of renal failure.Temporal macular thinning is a prominent sign associated with XLAS, suggesting that OCT measurements are essential in the diagnosis and prognosis of the disease. The L1649R mutation in the COL4A5 gene causes a relatively mild form of XLAS characterized by late-onset renal failure and less frequent, severe temporal macular thinning relative to other COL4A5 mutations. The pathological basis for the retinal abnormalities of XLAS remains to be established.

SUBMITTER: Ahmed F

PROVIDER: S-EPMC3746023 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Temporal macular thinning associated with X-linked Alport syndrome.

Ahmed Faisal F Kamae Kandon K KK Jones Denise J DJ Deangelis Margaret M MM Hageman Gregory S GS Gregory Martin C MC Bernstein Paul S PS

JAMA ophthalmology 20130601 6

<h4>Importance</h4>Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS).<h4>Objectives</h4>To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype.<h4>Design</h4>Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain O ...[more]

PMID: 23572034

Similar Datasets

Project description:Background and objectivesX-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism.Design, setting, participants, & measurementsIn total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) mRNA analysis using RT-PCR to detect RNA processing abnormalities.ResultsSix splicing consensus site mutations resulting in aberrant splicing patterns, one exonic mutation leading to exon skipping, and four deep intronic mutations producing cryptic splice site activation were identified. Interestingly, one case produced a cryptic splice site with a single nucleotide substitution in the deep intron that led to intronic exonization containing a stop codon; however, the patient showed a clearly milder phenotype for X-linked Alport syndrome in men with a truncating mutation. mRNA extracted from the kidney showed both normal and abnormal transcripts, with the normal transcript resulting in the milder phenotype. This novel mechanism leads to mild clinical characteristics.ConclusionsThis report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked Alport syndrome.

Dataset Information

Temporal macular thinning associated with X-linked Alport syndrome.

Publications

Temporal macular thinning associated with X-linked Alport syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets