title: Factors Affecting Phenotype Variability in a Family with CMT2B: Gender and LRSAM1 Genotype.
abstract: Charcot-Marie-Tooth disease type 2 (CMT2) is an autosomal dominant axonal neuropathy caused by mutations in various genes. The subtype CMT2B results from missense mutations in RAB7A, member RAS oncogene family gene, whereas missense mutations in the Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) gene cause CMT2P. We describe the genotype/phenotype analysis of a family in which a previously described mutation in the RAB7A gene and a novel mutation in the LRSAM1 gene were identified. In this family, none of the individuals had ulceromutilating features, and there was a marked variability in the age of onset. We discuss the possible etiology of the observed phenotypic variability including the role of gender and possible RAB7A/LRSAM1 gene interactions.
authors.affiliation: The Neuro Genetics Institute, Sharon Hill, Pa., USA.
authors.forename: Leema Reddy
authors.initials: LR
authors.lastname: Peddareddygari
authors.affiliation: The Neuro Genetics Institute, Sharon Hill, Pa., USA.
authors.forename: Kinsi
authors.initials: K
authors.lastname: Oberoi
authors.affiliation: The Neuro Genetics Institute, Sharon Hill, Pa., USA.
authors.forename: Jaasrini Reddy
authors.initials: JR
authors.lastname: Vellore
authors.affiliation: Neuroscience Institute, Saint Francis Medical Center, Trenton, N.J., USA.
authors.forename: Raji P
authors.initials: RP
authors.lastname: Grewal
keywords: Charcot-Marie-Tooth disease type 2B; Digeneic effect; Phenotype variability; RAB7A/LRSAM1 gene interactions