Premium
Déjerine‐Sottas syndrome with a silent nucleotide change of myelin protein zero gene
Author(s) -
Taioli Federica,
Cabrini Ilaria,
Cavallaro Tiziana,
Simonati Alessandro,
Testi Silvia,
Fabrizi Gian Maria
Publication year - 2011
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2011.00319.x
Subject(s) - frameshift mutation , exon , genetics , missense mutation , gene , nonsense mutation , proband , biology , mutation , transition (genetics) , microbiology and biotechnology , rna splicing , rna
Charcot‐Marie‐Tooth disease type 1B (CMT1B) and Déjerine‐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.