Paternal gender specificity and mild phenotypes in Charcot–Marie–Tooth type 1A patients with de novo 17p12 rearrangements

Abstract

Abstract Background Charcot–Marie–Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are developed by duplication and deletion of the 17p12 (PMP22) region, respectively. Methods De novo rates were determined in 211 CMT1A or HNPP trio families, and then, analyzed gender‐specific genetic features and clinical phenotypes of the de novo cases. Results This study identified 40 de novo cases (19.0%). Paternal origin was highly frequent compared to maternal origin (p = .005). Most de novo CMT1A rearrangements occurred between non‐sister chromatids (p = .003), but it was interesting that three of the four sister chromatids exchange cases were observed in the less frequent maternal origin. Paternal ages at the affected child births were slightly higher in the de novo CMT1A group than in the non‐de novo CMT1A control group (p = .0004). For the disability score of CMTNS, the de novo CMT1A group had a slightly lower value compared to the control group (p = .005). Electrophysiological studies showed no significant differences between the two groups. Conclusion This study suggests that de novo CMT1A patients tend to have milder symptoms and that the paternal ages at child births in the de novo group are higher than those of the non‐de novo group.

Keywords

• Charcot–Marie–Tooth disease 1A (CMT1A)
• de novo mutation
• gender specificity
• hereditary neuropathy with liability to pressure palsies (HNPP)