KEGG DISEASE: Distal hereditary motor neuropathies

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
  nt06541  Cytoskeleton in neurons
   H00856  Distal hereditary motor neuropathies
  nt06544  Neuroactive ligand signaling
   H00856  Distal hereditary motor neuropathies

Pathway

hsa04725

Cholinergic synapse

hsa04082

Neuroactive ligand signaling

Network

nt06515 Regulation of kinetochore-microtubule interactions
nt06541 Cytoskeleton in neurons
nt06544 Neuroactive ligand signaling

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]
(HMND15) BAG3 [HSA:9531] [KO:K09557]
(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:K28034]
(HMNR10) VRK1 [HSA:7443] [KO:K08816]
(HMNR11) RTN2 [HSA:6253] [KO:K20722]
(HMNX) ATP7A [HSA:538] [KO:K17686]

Other DBs

ICD-11:

8B61.4

MeSH:

D009134

OMIM:

182960 158590 608634 613376 600794 615575 158580 600175 617721 620080 620528 614751 619112 607641 621094 604320 605726 611067 614881 620011 619216 618912 620402 620542 620854 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

Reference

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

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:37907725 (HMND15)

Authors

de Fuenmayor-Fernandez de la Hoz CP, Lupo V, Bermejo-Guerrero L, Martin-Jimenez P, Hernandez-Lain A, Olive M, Gallardo E, Esteban-Perez J, Espinos C, Dominguez-Gonzalez C

Title

Distal hereditary motor neuronopathy as a new phenotype associated with variants in BAG3.

Journal

J Neurol 271:986-994 (2024)
DOI:10.1007/s00415-023-12039-9

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:38527963 (HMNR11)

Authors

Maroofian R, Sarraf P, O'Brien TJ, Kamel M, Cakar A, Elkhateeb N, Lau T, Patil SJ, Record CJ, Horga A, Essid M, Selim L, Benrhouma H, Ben Younes T, Zifarelli G, Pagnamenta AT, Bauer P, Khundadze M, Mirecki A, Kamel SM, Elmonem MA, Ghayoor Karimiani E, Jamshidi Y, Offiah AC, Rossor AM, Youssef-Turki IB, Hubner CA, Munot P, Reilly MM, Brown AEX, Nagy S, Houlden H

Title

Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Journal

Brain awae091 (2024)
DOI:10.1093/brain/awae091

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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