Vv. Ionasescu et al., MUTATIONS OF THE NONCODING REGION OF THE CONNEXIN32 GENE IN X-LINKED DOMINANT CHARCOT-MARIE-TOOTH NEUROPATHY, Neurology, 47(2), 1996, pp. 541-544
We studied two families with X-linked dominant Charcot-Marie-Tooth neu
ropathy. The clinical findings included onset around age 14 years, wit
h moderate weakness of feet extensors and palmar and dorsal interossei
, areflexia, distal hypesthesia, and slow progressivity. Motor nerve c
onduction velocities showed slowing (20 to 30 m/sec) and EMGs were nor
mal. Genetic linkage analysis revealed positive lod scores with the ma
rkers of the Xq13.1 region in family 2, but was noninformative in fami
ly 1. There were no point mutations in the connexin32 gene coding regi
on. Instead, family 1 revealed a T-to-G transversion at position -528
relative to the ATG start codon, whereas family 2 showed a C-to-T tran
sition at position -458. The first mutation is located in the nerve-sp
ecific connexin32 promoter just upstream of the transcription start si
te, the second is located in the 5' untranslated region of the mRNA.