| H00856 | |
| H number | H00856 |
| Name | Distal hereditary motor neuropathies |
| Description | Distal hereditary motor neuropathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT) [DS:H00264] and with juvenile forms of amyotrophic lateral sclerosis [DS:H00058] and hereditary spastic paraplegia [DS:H00266]. The causative genes with autosomal dominant, recessive, and X-linked patterns of inheritance have implicated proteins with diverse functions. Distal HMN are classified into phenotypic subtypes according to age at onset, mode of inheritance, and presence of additional features. |
| Category | Nervous system disease |
| Network | nt06515(H00856) Regulation of kinetochore-microtubule interactions |
| Gene | (HMN2A) HSPB8 [HSA:26353] [KO:K08879] (HMN2B) HSPB1 [HSA:3315] [KO:K04455] (HMN2C) HSPB3 [HSA:8988] [KO:K09544] (HMN2D) FBXO38 [HSA:81545] [KO:K10313] (HMN5A) GARS1 [HSA:2617] [KO:K01880] (HMN5B/DSMA6) REEP1 [HSA:65055] [KO:K17338] (HMN5C) BSCL2 [HSA:26580] [KO:K19365] (HMN6/DSMA1) IGHMBP2 [HSA:3508] [KO:K19036] (HMN7A) SLC5A7 [HSA:60482] [KO:K14387] (HMN7B) DCTN1 [HSA:1639] [KO:K04648] (HMN8) TRPV4 [HSA:59341] [KO:K04973] (HMN9) WARS1 [HSA:7453] [KO:K01867] (HMN10) EMILIN1 [HSA:11117] [KO:K24246] (DSMA2) SIGMAR1 [HSA:10280] [KO:K20719] (DSMA4) PLEKHG5 [HSA:57449] [KO:K19464] (DSMA5) DNAJB2 [HSA:3300] [KO:K09508] (DSMAX) ATP7A [HSA:538] [KO:K17686] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | Autosomal dominant inheritance include distal HMN1 and 2, characterized by juvenile and adult onset, respectively; HMN5, characterized by upper limb involvement; HMN7, with vocal cord paralysis; and HMN8. HMN has also been referred to as distal spinal muscular atrophy (DSMA). DSMA here refers to the autosomal recessive forms of HMN. See also H00455 Spinal muscular atrophy (SMA). |
| Other DBs | ICD-11: 8B61.4 ICD-10: G12.1 G12.2 MeSH: D009134 OMIM: 182960 158590 608634 613376 615575 600794 614751 619112 604320 158580 607641 600175 617721 620080 605726 611067 614881 620011 300489 |
| Reference | PMID:22028385 AUTHORS Rossor AM, Kalmar B, Greensmith L, Reilly MM TITLE The distal hereditary motor neuropathies. JOURNAL J Neurol Neurosurg Psychiatry 83:6-14 (2012) DOI:10.1136/jnnp-2011-300952 PMID:19917815 AUTHORS Reilly MM, Shy ME TITLE Diagnosis and new treatments in genetic neuropathies. JOURNAL J Neurol Neurosurg Psychiatry 80:1304-14 (2009) DOI:10.1136/jnnp.2008.158295 PMID:15122253 (HMN2A) AUTHORS Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V TITLE Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. JOURNAL Nat Genet 36:597-601 (2004) DOI:10.1038/ng1328 PMID:15122254 (HMN2B) AUTHORS Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V TITLE Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. JOURNAL Nat Genet 36:602-6 (2004) DOI:10.1038/ng1354 PMID:20142617 (HMN2C) AUTHORS Kolb SJ, Snyder PJ, Poi EJ, Renard EA, Bartlett A, Gu S, Sutton S, Arnold WD, Freimer ML, Lawson VH, Kissel JT, Prior TW TITLE Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. JOURNAL Neurology 74:502-6 (2010) DOI:10.1212/WNL.0b013e3181cef84a PMID:24207122 (HMN2D) AUTHORS Sumner CJ, d'Ydewalle C, Wooley J, Fawcett KA, Hernandez D, Gardiner AR, Kalmar B, Baloh RH, Gonzalez M, Zuchner S, Stanescu HC, Kleta R, Mankodi A, Cornblath DR, Boylan KB, Reilly MM, Greensmith L, Singleton AB, Harms MB, Rossor AM, Houlden H TITLE A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. JOURNAL Am J Hum Genet 93:976-83 (2013) DOI:10.1016/j.ajhg.2013.10.006 PMID:12690580 (HMN5A) AUTHORS Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED TITLE Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. JOURNAL Am J Hum Genet 72:1293-9 (2003) DOI:10.1086/375039 PMID:22703882 (HMN5B) AUTHORS Beetz C, Pieber TR, Hertel N, Schabhuttl M, Fischer C, Trajanoski S, Graf E, Keiner S, Kurth I, Wieland T, Varga RE, Timmerman V, Reilly MM, Strom TM, Auer-Grumbach M TITLE Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V. JOURNAL Am J Hum Genet 91:139-45 (2012) DOI:10.1016/j.ajhg.2012.05.007 PMID:14981520 (HMN5C) AUTHORS Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Horl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Van den Bergh P, Verellen C, Van Maldergem L, Merlini L, De Jonghe P, Timmerman V, Crosby AH, Wagner K TITLE Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. JOURNAL Nat Genet 36:271-6 (2004) DOI:10.1038/ng1313 PMID:11528396 (HMN6/DSMA1) AUTHORS Grohmann K, Schuelke M, Diers A, Hoffmann K, Lucke B, Adams C, Bertini E, Leonhardt-Horti H, Muntoni F, Ouvrier R, Pfeufer A, Rossi R, Van Maldergem L, Wilmshurst JM, Wienker TF, Sendtner M, Rudnik-Schoneborn S, Zerres K, Hubner C TITLE Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. JOURNAL Nat Genet 29:75-7 (2001) DOI:10.1038/ng703 PMID:23141292 (HMN7A) AUTHORS Barwick KE, Wright J, Al-Turki S, McEntagart MM, Nair A, Chioza B, Al-Memar A, Modarres H, Reilly MM, Dick KJ, Ruggiero AM, Blakely RD, Hurles ME, Crosby AH TITLE Defective presynaptic choline transport underlies hereditary motor neuropathy. JOURNAL Am J Hum Genet 91:1103-7 (2012) DOI:10.1016/j.ajhg.2012.09.019 PMID:12627231 (HMN7B) AUTHORS Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floeter MK, Bidus K, Drayna D, Oh SJ, Brown RH Jr, Ludlow CL, Fischbeck KH TITLE Mutant dynactin in motor neuron disease. JOURNAL Nat Genet 33:455-6 (2003) DOI:10.1038/ng1123 PMID:20037588 (HMN8) AUTHORS Auer-Grumbach M, Olschewski A, Papic L, Kremer H, McEntagart ME, Uhrig S, Fischer C, Frohlich E, Balint Z, Tang B, Strohmaier H, Lochmuller H, Schlotter-Weigel B, Senderek J, Krebs A, Dick KJ, Petty R, Longman C, Anderson NE, Padberg GW, Schelhaas HJ, van Ravenswaaij-Arts CM, Pieber TR, Crosby AH, Guelly C TITLE Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. JOURNAL Nat Genet 42:160-4 (2010) DOI:10.1038/ng.508 PMID:28369220 (HMN9) AUTHORS Tsai PC, Soong BW, Mademan I, Huang YH, Liu CR, Hsiao CT, Wu HT, Liu TT, Liu YT, Tseng YT, Lin KP, Yang UC, Chung KW, Choi BO, Nicholson GA, Kennerson ML, Chan CC, De Jonghe P, Cheng TH, Liao YC, Zuchner S, Baets J, Lee YC TITLE A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. JOURNAL Brain 140:1252-1266 (2017) DOI:10.1093/brain/awx058 PMID:26462740 (HMN10) AUTHORS Capuano A, Bucciotti F, Farwell KD, Tippin Davis B, Mroske C, Hulick PJ, Weissman SM, Gao Q, Spessotto P, Colombatti A, Doliana R TITLE Diagnostic Exome Sequencing Identifies a Novel Gene, EMILIN1, Associated with Autosomal-Dominant Hereditary Connective Tissue Disease. JOURNAL Hum Mutat 37:84-97 (2016) DOI:10.1002/humu.22920 PMID:26078401 (DSMA2) AUTHORS Li X, Hu Z, Liu L, Xie Y, Zhan Y, Zi X, Wang J, Wu L, Xia K, Tang B, Zhang R TITLE A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy. JOURNAL Neurology 84:2430-7 (2015) DOI:10.1212/WNL.0000000000001680 PMID:17564964 (DSMA4) AUTHORS Maystadt I, Rezsohazy R, Barkats M, Duque S, Vannuffel P, Remacle S, Lambert B, Najimi M, Sokal E, Munnich A, Viollet L, Verellen-Dumoulin C TITLE The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset. JOURNAL Am J Hum Genet 81:67-76 (2007) DOI:10.1086/518900 PMID:22522442 (DSMA5) AUTHORS Blumen SC, Astord S, Robin V, Vignaud L, Toumi N, Cieslik A, Achiron A, Carasso RL, Gurevich M, Braverman I, Blumen N, Munich A, Barkats M, Viollet L TITLE A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone mutation. JOURNAL Ann Neurol 71:509-19 (2012) DOI:10.1002/ana.22684 PMID:27066569 (DSMA6) AUTHORS Schottmann G, Seelow D, Seifert F, Morales-Gonzalez S, Gill E, von Au K, von Moers A, Stenzel W, Schuelke M TITLE Recessive REEP1 mutation is associated with congenital axonal neuropathy and diaphragmatic palsy. JOURNAL Neurol Genet 1:e32 (2015) DOI:10.1212/NXG.0000000000000032 PMID:20170900 (DSMAX) AUTHORS Kennerson ML, Nicholson GA, Kaler SG, Kowalski B, Mercer JF, Tang J, Llanos RM, Chu S, Takata RI, Speck-Martins CE, Baets J, Almeida-Souza L, Fischer D, Timmerman V, Taylor PE, Scherer SS, Ferguson TA, Bird TD, De Jonghe P, Feely SM, Shy ME, Garbern JY TITLE Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. JOURNAL Am J Hum Genet 86:343-52 (2010) DOI:10.1016/j.ajhg.2010.01.027 |