Genetic analysis of novel hereditary neuropathy mapping to chromosome 1

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kurume University
• Principal Investigator: SHIROH MIURA 久留米大学, 医学部, 講師 (00441650)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: IQGAP3 / 遺伝性ニューロパチー / エクソーム / 連鎖解析

Outline of Final Research Achievements

To identify the causative variation for a clinically and genetically new type of autosomal dominant motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough, we studied a Japanese pedigree with the disease consisted with 19 family members including 9 patients in 5 generations. On multipoint linkage analysis of the pedigree, maximum LOD scores of > 2.0 was obtained on 1p13.3-q23 (LOD = 2.24). The exome sequencing upon seven patients and one healthy relative from the pedigree revealed one causative single nucleotide variant (SNV) located in IQGAP3 which is associated with neurite outgrowth. The SNV is highly conserved among vertebrates. Real time quantitative PCR analysis of peripheral blood samples showed the mRNA expression level of IQGAP3 was significantly higher in a patient. The SNV alters the splicing of IQGAP3 and also located within a non-coding RNA which may affect the expression of IQGAP3.

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