Unexpectedly mild phenotype in an ataxic family with a two-base deletion in the APTX gene
| Autor: | Hiroya Inoue, Makito Hirano, Susumu Kusunoki, Hikaru Sakamoto, Yusaku Nakamura, Ryusuke Matsumura, Shuichi Ueno, Kazumasa Saigoh |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Ataxia aptX Biology Frameshift mutation 03 medical and health sciences Exon Fatal Outcome 0302 clinical medicine medicine Humans Protein Isoforms Missense mutation RNA Messenger Oculomotor apraxia Frameshift Mutation Gene Cells Cultured Aged Sequence Deletion Aprataxin Genetics Nuclear Proteins Middle Aged medicine.disease Molecular biology DNA-Binding Proteins Phenotype 030104 developmental biology Neurology Female Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Journal of the Neurological Sciences. 378:75-79 |
| ISSN: | 0022-510X |
| DOI: | 10.1016/j.jns.2017.04.049 |
| Popis: | Introduction Early onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia 1 (AOA1) is an autosomal recessive disorder caused by mutations in the APTX gene. In contrast to the recent progress on the molecular mechanism of aprataxin in DNA repair, the genotype and phenotype correlation has not been fully established. A previous study demonstrated that patients with truncation mutations had earlier onset of disease than those with missense mutations Methods Genomic DNA analysis was performed in a consanguineous family with relatively late-onset EAOH/AOA1. In addition, mRNA and protein analyses were performed. Results The proband of the family had a homozygous two-base deletion in the middle of exon 3. Reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of mRNA revealed an aberrantly spliced mRNA with a cryptic splice site located four bases upstream of the deletion site. The newly identified mRNA retained a frameshift mutation and encoded a truncated protein. Immunoblot analysis did not detect the truncated protein in the patient's fibroblasts, possibly because it was unstable. Conclusions Although patients with truncation mutations had an earlier onset of disease, our findings suggest that patients with a truncation mutation resulting in an undetectable protein level can also have a later onset of disease. |
| Databáze: | OpenAIRE |
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