KEGG   DISEASE: Distal hereditary motor neuropathies
Entry
H00856                      Disease                                
Name
Distal hereditary motor neuropathies
  Subgroup
Autosomal dominant distal hereditary motor neuropathy (HMND)
Autosomal recessive distal hereditary motor neuropathy (HMNR)
X-linked distal hereditary motor neuropathy (HMNX)
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
Brite
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Motor neuron diseases or related disorders
   8B61  Spinal muscular atrophy
    H00856  Distal hereditary motor neuropathies
Pathway-based classification of diseases [BR:br08402]
 Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H00856  Distal hereditary motor neuropathies
Network
nt06515 Regulation of kinetochore-microtubule interactions
Gene
(HMND2) HSPB8 [HSA:26353] [KO:K08879]
(HMND3) HSPB1 [HSA:3315] [KO:K04455]
(HMND4) HSPB3 [HSA:8988] [KO:K09544]
(HMND5) GARS1 [HSA:2617] [KO:K01880]
(HMND6) FBXO38 [HSA:81545] [KO:K10313]
(HMND7) SLC5A7 [HSA:60482] [KO:K14387]
(HMND8) TRPV4 [HSA:59341] [KO:K04973]
(HMND9) WARS1 [HSA:7453] [KO:K01867]
(HMND10) EMILIN1 [HSA:11117] [KO:K24246]
(HMND11) SPTAN1 [HSA:6709] [KO:K06114]
(HMND12/HMNR6) REEP1 [HSA:65055] [KO:K17338]
(HMND13) BSCL2 [HSA:26580] [KO:K19365]
(HMND14) DCTN1 [HSA:1639] [KO:K04648]
(HMNR1) IGHMBP2 [HSA:3508] [KO:K19036]
(HMNR2) SIGMAR1 [HSA:10280] [KO:K20719]
(HMNR4) PLEKHG5 [HSA:57449] [KO:K19464]
(HMNR5) DNAJB2 [HSA:3300] [KO:K09508]
(HMNR7) VWA1 [HSA:64856] [KO:K24507]
(HMNR8) SORD [HSA:6652] [KO:K00008]
(HMNR9) COQ7 [HSA:10229] [KO:K06134]
(HMNR10) VRK1 [HSA:7443] [KO:K08816]
(HMNX) ATP7A [HSA:538] [KO:K17686]
Other DBs
ICD-11: 8B61.4
ICD-10: G12.1 G12.2
MeSH: D009134
OMIM: 182960 158590 608634 613376 600794 615575 158580 600175 617721 620080 620528 614751 619112 607641 604320 605726 611067 614881 620011 619216 618912 620402 620542 300489
Reference
  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
Reference
  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
Reference
PMID:15122253 (HMND2)
  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
Reference
PMID:15122254 (HMND3)
  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
Reference
PMID:20142617 (HMND4)
  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
Reference
PMID:12690580 (HMND5)
  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
Reference
PMID:24207122 (HMND6)
  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
Reference
PMID:23141292 (HMND7)
  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
Reference
PMID:20037588 (HMND8)
  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
Reference
PMID:28369220 (HMND9)
  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
Reference
PMID:26462740 (HMND10)
  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
Reference
PMID:31332438 (HMND11)
  Authors
Beijer D, Deconinck T, De Bleecker JL, Dotti MT, Malandrini A, Urtizberea JA, Zulaica M, Lopez de Munain A, Asselbergh B, De Jonghe P, Baets J
  Title
Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy.
  Journal
Brain 142:2605-2616 (2019)
DOI:10.1093/brain/awz216
Reference
PMID:22703882 (HMND12)
  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
Reference
PMID:14981520 (HMND13)
  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
Reference
PMID:12627231 (HMND14)
  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
Reference
PMID:11528396 (HMNR1)
  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
Reference
PMID:26078401 (HMNR2)
  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
Reference
PMID:17564964 (HMNR4)
  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
Reference
PMID:22522442 (HMNR5)
  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
Reference
PMID:27066569 (HMNR6)
  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
Reference
PMID:33459760 (HMNR7)
  Authors
Deschauer M, Hengel H, Rupprich K, Kreiss M, Schlotter-Weigel B, Grimmel M, Admard J, Schneider I, Alhaddad B, Gazou A, Sturm M, Vorgerd M, Balousha G, Balousha O, Falna M, Kirschke JS, Kornblum C, Jordan B, Kraya T, Strom TM, Weis J, Schols L, Schara U, Zierz S, Riess O, Meitinger T, Haack TB
  Title
Bi-allelic truncating mutations in VWA1 cause neuromyopathy.
  Journal
Brain 144:574-583 (2021)
DOI:10.1093/brain/awaa418
Reference
PMID:32367058 (HMNR8)
  Authors
Cortese A, Zhu Y, Rebelo AP, Negri S, Courel S, Abreu L, Bacon CJ, Bai Y, Bis-Brewer DM, Bugiardini E, Buglo E, Danzi MC, Feely SME, Athanasiou-Fragkouli A, Haridy NA, Isasi R, Khan A, Laura M, Magri S, Pipis M, Pisciotta C, Powell E, Rossor AM, Saveri P, Sowden JE, Tozza S, Vandrovcova J, Dallman J, Grignani E, Marchioni E, Scherer SS, Tang B, Lin Z, Al-Ajmi A, Schule R, Synofzik M, Maisonobe T, Stojkovic T, Auer-Grumbach M, Abdelhamed MA, Hamed SA, Zhang R, Manganelli F, Santoro L, Taroni F, Pareyson D, Houlden H, Herrmann DN, Reilly MM, Shy ME, Zhai RG, Zuchner S
  Title
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.
  Journal
Nat Genet 52:473-481 (2020)
DOI:10.1038/s41588-020-0615-4
Reference
PMID:36454683 (HMNR9)
  Authors
Jacquier A, Theuriet J, Fontaine F, Mosbach V, Lacoste N, Ribault S, Risson V, Carras J, Coudert L, Simonet T, Latour P, Stojkovic T, Piard J, Cosson A, Lesca G, Bouhour F, Allouche S, Puccio H, Pegat A, Schaeffer L
  Title
Homozygous COQ7 mutation: a new cause of potentially treatable distal hereditary motor neuropathy.
  Journal
Brain 146:3470-3483 (2023)
DOI:10.1093/brain/awac453
Reference
PMID:24126608 (HMNR10)
  Authors
Gonzaga-Jauregui C, Lotze T, Jamal L, Penney S, Campbell IM, Pehlivan D, Hunter JV, Woodbury SL, Raymond G, Adesina AM, Jhangiani SN, Reid JG, Muzny DM, Boerwinkle E, Lupski JR, Gibbs RA, Wiszniewski W
  Title
Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly.
  Journal
JAMA Neurol 70:1491-8 (2013)
DOI:10.1001/jamaneurol.2013.4598
Reference
PMID:20170900 (HMNRX)
  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

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