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Disease Report for: Hereditary motor and sensory neuropathy, LOM Type

Alternative name(s)|HMNSL
Charcot-Marie-Tooth disease, Type 4D
Charcot-Marie-Tooth neuropathy, Type 4D
Mutation|8 mutations (e.g. : 6.25kbdup_human-NDRG1, H247TfsX74_human-NDRG1, IVS8-1G>A_human-NDRG1... more)
OMIM: |601455, 605262

(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)

    Title: Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies
    Dohrn MF, Glockle N, Mulahasanovic L, Heller C, Mohr J, Bauer C, Riesch E, Becker A, Battke F and Biskup S <23 more author(s)>
    Ref: Journal of Neurochemistry, 143:507, 2017 : PubMed


    Title: Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D
    Li LX, Liu GL, Liu ZJ, Lu C, Wu ZY
    Ref: Hum Mutat, 38:1569, 2017 : PubMed


    Title: A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom
    Piscosquito G, Magri S, Saveri P, Milani M, Ciano C, Farina L, Taroni F, Pareyson D
    Ref: J Peripher Nerv Syst, 22:47, 2017 : PubMed


    Title: Clinical, electrophysiological and pathological findings in a patient with Charcot-Marie-Tooth disease 4D caused by the NDRG1 Lom mutation
    Luigetti M, Taroni F, Milani M, Del Grande A, Romano A, Bisogni G, Conte A, Contaldo I, Mercuri E, Sabatelli M
    Ref: Journal of Neurology Sci, 345:271, 2014 : PubMed


    Title: Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D
    Okamoto Y, Goksungur MT, Pehlivan D, Beck CR, Gonzaga-Jauregui C, Muzny DM, Atik MM, Carvalho CM, Matur Z and Lupski JR <6 more author(s)>
    Ref: Genet Med, 16:386, 2014 : PubMed


    Title: CMT4D (NDRG1 mutation): genotype-phenotype correlations
    Ricard E, Mathis S, Magdelaine C, Delisle MB, Magy L, Funalot B, Vallat JM
    Ref: J Peripher Nerv Syst, 18:261, 2013 : PubMed


    Title: Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth
    Sevilla T, Martinez-Rubio D, Marquez C, Paradas C, Colomer J, Jaijo T, Millan J, Palau F, Espinos C, Millan JM
    Ref: Clin Genet, 83:565, 2013 : PubMed


    Title: The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4
    Claramunt R, Sevilla T, Lupo V, Cuesta A, Millan JM, Vilchez JJ, Palau F, Espinos C
    Ref: Clin Genet, 71:343, 2007 : PubMed


    Title: NDRG1-linked Charcot-Marie-Tooth disease (CMT4D) with central nervous system involvement
    Echaniz-Laguna A, Degos B, Bonnet C, Latour P, Hamadouche T, Levy N, Leheup B
    Ref: Neuromuscular Disorders, 17:163, 2007 : PubMed


    Title: Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease
    Hunter M, Bernard R, Freitas E, Boyer A, Morar B, Martins IJ, Tournev I, Jordanova A, Guergelcheva V and Kalaydjieva L <9 more author(s)>
    Ref: Hum Mutat, 22:129, 2003 : PubMed


    Title: N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom
    Kalaydjieva L, Gresham D, Gooding R, Heather L, Baas F, de Jonge R, Blechschmidt K, Angelicheva D, Chandler D and Thomas PK <3 more author(s)>
    Ref: American Journal of Human Genetics, 67:47, 2000 : PubMed


    Title: Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and malignant cells
    Park H, Adams MA, Lachat P, Bosman F, Pang SC, Graham CH
    Ref: Biochemical & Biophysical Research Communications, 276:321, 2000 : PubMed


    Title: Ultrastructural changes in peripheral nerve in hereditary motor and sensory neuropathy-Lom
    King RH, Tournev I, Colomer J, Merlini L, Kalaydjieva L, Thomas PK
    Ref: Neuropathol Appl Neurobiol, 25:306, 1999 : PubMed


    Title: Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells
    Piquemal D, Joulia D, Balaguer P, Basset A, Marti J, Commes T
    Ref: Biochimica & Biophysica Acta, 1450:364, 1999 : PubMed


    Title: N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant
    Shimono A, Okuda T, Kondoh H
    Ref: Mech Dev, 83:39, 1999 : PubMed


    Title: Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings
    Kalaydjieva L, Nikolova A, Turnev I, Petrova J, Hristova A, Ishpekova B, Petkova I, Shmarov A, Stancheva S and Thomas PK <5 more author(s)>
    Ref: Brain, 121 ( Pt 3):399, 1998 : PubMed


    Title: Hereditary motor and sensory neuropathy Lom type in an Italian Gypsy family
    Merlini L, Villanova M, Sabatelli P, Trogu A, Malandrini A, Yanakiev P, Maraldi NM, Kalaydjieva L
    Ref: Neuromuscular Disorders, 8:182, 1998 : PubMed


    Title: Cap43, a novel gene specifically induced by Ni2+ compounds
    Zhou D, Salnikow K, Costa M
    Ref: Cancer Research, 58:2182, 1998 : PubMed


    Title: A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms
    van Belzen N, Dinjens WNM, Diesveld MPG, Groen NA, van der Made ACJ, Nozawa Y, Vlietstra R, Trapman J, Bosman FT and van der Made AC <2 more author(s)>
    Ref: Lab Invest, 77:85, 1997 : PubMed


    Title: A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8
    Ionasescu VV, Kimura J, Searby CC, Smith WL, Jr., Ross MA, Ionasescu R
    Ref: Muscle & Nerve, 19:319, 1996 : PubMed


    Title: Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24
    Kalaydjieva L, Hallmayer J, Chandler D, Savov A, Nikolova A, Angelicheva D, King RH, Ishpekova B, Honeyman K and Thomas PK <11 more author(s)>
    Ref: Nat Genet, 14:214, 1996 : PubMed


    Title: Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes
    Kokame K, Kato H, Miyata T
    Ref: Journal of Biological Chemistry, 271:29659, 1996 : PubMed


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