Inheritance of CMT1A duplication from a mosaic father

Abstract

We describe a case with molecular duplication of chromosome 17 (p11.2-p12) whose duplicated chromosome was inherited whose a mosaic father. The patient has clinical manifestations consistent with Charcot-Marie-Tooth disease type 1A (CMT1A), while the mosaic father has minimal findings of CMT1A. The father was found to be homozygous with DNA markers VAW409R3A (D17S122) and p132G8RI (PMP-22) which are duplicated in CMT1A cases. Fluorescence in situ hybridisation (FISH) analysis with YAC clone 49H7 confirmed the duplication in the affected patient and diagnosed the mosaicism in his father. These findings based on clinical diagnosis and FISH analysis suggest that the mosaicism may have occurred early in embryogenesis leading to the disease in the father. This is the only reported case of CMT1A with transmission from a mildly affected mosaic father.