Kulshrestha R, Burton-Jones S, Antoniadi T, Rogers M, Jaunmuktane Z, Brandner S, Kiely N, Manuel R, Willis T
Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.
Bristol Genetics Laboratory, North Bristol NHS Trust, Southmead Hospital, Bristol, UK.
Neuromuscul Disord. 2017 Aug;27(8):766-770. doi: 10.1016/j.nmd.2017.05.001. Epub 2017 May 4.
X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously.
X连锁型夏科-马里-图斯病（CMT）是CMT的第二大常见病因，通常由缝隙连接蛋白β1（GJB1）基因突变引起。该基因具有神经特异性P2启动子，它与SOX10和EGR2基因协同作用以启动转录。已知该区域的突变会导致施万细胞功能障碍。我们在临床中发现了一个X连锁型周围神经病的大家族。靶向基因panel检测的二代测序鉴定出一个上游外显子剪接缺失，该缺失从核苷酸c.-5413延伸至约-c.-49。这与GJB1基因3'UTR中c.*218-*249位置的32个核苷酸序列相匹配。缺失片段包括整个P2启动子区域。该缺失与疾病共分离。据我们所知，此前尚未报道过单独的P2启动子缺失作为CMT病因的情况。
