Dataset Information

Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine.

ABSTRACT: BACKGROUND:Alport syndrome is a primary basement membrane disorder arising from mutations in genes encoding the type IV collagen protein family. It is a genetically heterogeneous disease with different mutations and forms of inheritance that presents with renal affection, hearing loss and eye defects. Several new mutations related to X-linked forms have been previously determined. METHODS:We report the case of a 12 years old male and his family diagnosed with Alport syndrome after genetic analysis was performed. RESULT:A new mutation determining a nucleotide change c.3614G > T (p.Gly1205Val) in hemizygosis in the COL4A5 gene was found. This molecular defect has not been previously described. CONCLUSION:Molecular biology has helped us to comprehend the mechanisms of pathophysiology in Alport syndrome. Genetic analysis provides the only conclusive diagnosis of the disorder at the moment. Our contribution with a new mutation further supports the need of more sophisticated molecular methods to increase the mutation detection rates with lower costs and less time.

SUBMITTER: Anton-Martin P

PROVIDER: S-EPMC3620815 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine.

Antón-Martín Pilar P Aparicio López Cristina C Ramiro-León Soraya S Santillán Garzón Sonia S Santos-Simarro Fernando F Gil-Fournier Belén B

Clinical medicine insights. Pediatrics 20120628

<h4>Background</h4>Alport syndrome is a primary basement membrane disorder arising from mutations in genes encoding the type IV collagen protein family. It is a genetically heterogeneous disease with different mutations and forms of inheritance that presents with renal affection, hearing loss and eye defects. Several new mutations related to X-linked forms have been previously determined.<h4>Methods</h4>We report the case of a 12 years old male and his family diagnosed with Alport syndrome after ...[more]

PMID: 23641165

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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

Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine.

Publications

Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine.

Similar Datasets

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