Hereditary motor and sensory neuropathy, LOM Type

Alternative name(s) : HMNSL, NMSL, Charcot-Marie-Tooth disease, Type 4D, CMT4D, Charcot-Marie-Tooth neuropathy, Type 4D

Gene_locus : human-NDRG1

Mutation : 8 mutations R148X_human-NDRG1 Q185X_human-NDRG1 IVS8-1G>A_human-NDRG1 6.25kbdup_human-NDRG1 S317RfsX4_human-NDRG1 H247TfsX74_human-NDRG1 R234Q_human-NDRG1 L146P_human-NDRG1

OMIM : 601455 , 605262

Comment

(from OMIM) Autosomal recessive peripheral neuropathies are relatively rare but are clinically more severe than autosomal dominant forms of Charcot-Marie-Tooth disease (CMT). The Lom form of hereditary motor and sensory neuropathy (HMSNL), or CMT4D, is one such disorder. Kalaydjieva et al. (1996) described an autosomal recessive peripheral neuropathy with deafness and unusual neuropathologic features, initially identified in 14 affected individuals from the Gypsy community of Lom, a small town on the Danube river in the northwest of Bulgaria. They proposed to refer to the disorder as 'hereditary motor and sensory neuropathy-Lom' (HMSNL). Kalaydjieva et al. (1996) stated that HMSNL is characterized by distal muscle wasting and atrophy, foot and hand deformities, tendon areflexia, and sensory loss. Onset is in the first decade and most patients become severely disabled in the fifth decade. Deafness is an invariant feature of the phenotype and usually develops in the third decade. HMSNL shows features of Schwann cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axon-glia interactions play a major role in its pathogenesis. Kalaydjieva et al. (2000) identified the founder HMSNL mutation, a nonsense arg148-to-ter mutation in the NDRG1 gene. Another gene of the same family ratno-ndr4 (Bdm1) is associated with hot water epilepsy (Bhaduri et al. 2003)