Dejerine-Sottas syndrome with a silent nucleotide change of myelin protein zero gene

作者：Taioli Federica; Cabrini Ilaria; Cavallaro Tiziana; Simonati Alessandro; Testi Silvia; Fabrizi Gian Maria^*

来源：Journal of the Peripheral Nervous System, 2011, 16(1): 59-64.

DOI：10.1111/j.1529-8027.2011.00319.x

• aberrant splicing
• Dejerine-Sottas syndrome
• myelin protein zero

Charcot-Marie-Tooth disease type 1B (CMT1B) and Dejerine-Sottas syndrome type B (DSSB) are caused by missense or frameshift mutations of myelin protein zero (MPZ) gene. We identified an apparently silent synonymous c.411C > T transition in MPZ exon 3 (p.Gly137Gly) which segregated with DSS in a two-generation pedigree. Retro-transcriptional analysis of MPZ in the proband's archive sural nerve biopsy identified an r.410_448del mutant transcript which resulted from an activated cryptic splice site in exon 3 and led to an in-frame partial deletion of exon 3 (p.Gly137_Lys149del). Quantitative real-time polymerase chain reaction (QRT-PCR) compared with two unrelated CMT1B nerves carrying a frameshift c.306delA mutation (p.Asp104ThrfsX13) indicated that the r.410_448del was stable differing from the p.Asp104ThrfsX13-associated transcript which was subjected to nonsense-mediated decay. The report highlighted the possible pathogenic role of synonymous MPZ mutations and difficulties in interpreting results from routine mutational screenings.

• 出版日期2011-3