Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis.
We report on two sisters with Dejerine-Sottas syndrome (DSS) who had a heterozygous Gly 167 Arg mutation in the myelin protein zero (MPZ) gene and hereditary stomatocytosis (HSt). Genetic haplotype analysis suggested that the allele with the MPZ gene mutation originated from maternal lineage. However, the parents, who were normal clinically and electrophysiologically, had no mutation in the MPZ gene. Therefore, the MPZ gene mutation in these sisters was due to germline mosaicism of the MPZ gene in their mother. Stomatocytosis was detected in their mother and a sister who had no neurological symptoms, and therefore autosomal dominant HSt was suspected in this family. As stomatocytosis is very severe in our patients with DDS, we speculate that the association of DSS with stomatocytosis is coincidental but may have additively affected erythrocyte morphology. To our knowledge, these are the first familial cases of DSS with a mutation due to germline mosaicism of the MPZ gene to be reported.
Takashima
H
H
Third Department of Internal Medicine, Kagoshima University School of Medicine, Japan.
Nakagawa
M
M
Kanzaki
A
A
Yawata
Y
Y
Horikiri
T
T
Matsuzaki
T
T
Suehara
M
M
Izumo
S
S
Osame
M
M
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D004906:Erythrocyte Count; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000502:physiology / Q000648:ultrastructure; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009030:Mosaicism / Q000235:genetics*; D009154:Mutation / Q000502:physiology; D018993:Myelin P0 Protein / Q000235:genetics*; D010375:Pedigree; D013497:Sural Nerve / Q000473:pathology
D018993:Myelin P0 Protein; D004247:DNA