Intronic variant in IQGAP3 associated with hereditary neuropathy with proximal lower dominancy, urinary disturbance, and paroxysmal dry cough

Autor: Kengo Kosaka, Eiji Matsuura, Shin Ichiro Mori, Shiroh Miura, Ryuta Fujioka, Hirotomo Saitsu, Ken Yamamoto, Kazuhito Noda, Fujio Umehara, Tomofumi Shimojo, Hiroki Shibata, Toru Iwaki
Rok vydání: 2020
Předmět:
Zdroj: Journal of Human Genetics. 65:717-725
ISSN: 1435-232X
1434-5161
DOI: 10.1038/s10038-020-0761-7
Popis: In 2008, we reported a clinically and genetically new type of autosomal dominant disorder of motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough. To identify the nucleotide variant causative of this disease, we reanalyzed the linkage of the original Japanese pedigree including seven newly ascertained subjects with updated information. We assigned the locus of the disease to 1p13.3-q23 (maximum logarithm-of-odds score = 2.71). Exome sequencing for five patients and one healthy relative from the pedigree revealed 2526 patient-specific single-nucleotide variants (SNVs). By rigorous filtering processes using public databases, our linkage results, and functional prediction, followed by Sanger sequencing of the pedigree and 520 healthy Japanese individuals, we identified an intronic SNV in IQGAP3, a gene known to be associated with neurite outgrowth. Upon pathological examination of the sural nerve, moderate, chronic, mainly axonal neuropathy was observed. By histochemical analyses, we observed a patient-specific increase of IQGAP3 expression in the sural nerve. We concluded that the variant of IQGAP3 is associated with the disease in our pedigree.
Databáze: OpenAIRE
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