Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Peter Tang
 + 460 word(s) 460 2020-12-15 07:22:14

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Tang, P. DHMN-V. Encyclopedia. Available online: https://encyclopedia.pub/entry/6042 (accessed on 17 May 2024).
Tang P. DHMN-V. Encyclopedia. Available at: https://encyclopedia.pub/entry/6042. Accessed May 17, 2024.
Tang, Peter. "DHMN-V" Encyclopedia, https://encyclopedia.pub/entry/6042 (accessed May 17, 2024).
Tang, P. (2021, January 04). DHMN-V. In Encyclopedia. https://encyclopedia.pub/entry/6042
Tang, Peter. "DHMN-V." Encyclopedia. Web. 04 January, 2021.
DHMN-V
Edit
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/distal-hereditary-motor-neuropathy-type-v

Distal hereditary motor neuropathy, type V is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement of the hands and feet.

genetic conditions

1. Introduction

Symptoms of distal hereditary motor neuropathy, type V usually begin during adolescence, but onset varies from infancy to the mid-thirties. Cramps in the hand brought on by exposure to cold temperatures are often the initial symptom.

The characteristic features of distal hereditary motor neuropathy, type V are weakness and wasting (atrophy) of muscles of the hand, specifically on the thumb side of the index finger and in the palm at the base of the thumb. Foot abnormalities, such as a high arch (pes cavus), are also common, and some affected individuals eventually develop problems with walking (gait disturbance). People with this disorder have normal life expectancies.

2. Frequency

The incidence of distal hereditary motor neuropathy, type V is unknown. Only a small number of cases have been reported.

3. Causes

Mutations in the BSCL2 and GARS1 genes cause distal hereditary motor neuropathy, type V.

The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Mutations in the BSCL2 gene likely alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum, which is a structure inside the cell that is involved in protein processing and transport. This accumulation likely damages and kills motor neurons (specialized nerve cells in the brain and spinal cord that control muscle movement), leading to muscle weakness in the hands and feet.

The GARS1 gene provides instructions for making an enzyme called glycyl-tRNA synthetase, which is involved in the production (synthesis) of proteins. It is unclear how GARS1 gene mutations lead to distal hereditary motor neuropathy, type V. The mutations probably reduce the activity of glycyl-tRNA synthetase. A reduction in the activity of this enzyme may impair transmission of nerve impulses. As a result, nerve cells slowly lose the ability to communicate with muscles in the hands and feet.

Mutations in other genes may also cause distal hereditary motor neuropathy, type V.

3.1. The genes associated with Distal hereditary motor neuropathy, type V

  • BSCL2
  • GARS1
  • REEP1

4. Inheritance

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Some people who have the altered gene never develop the condition, a situation known as reduced penetrance.

5. Other Names for This Condition

  • distal hereditary motor neuronopathy type 5
  • distal hereditary motor neuronopathy, type V
  • distal spinal muscular atrophy, type V
  • DSMAV
  • HMN V
  • spinal muscular atrophy, distal type V
  • spinal muscular atrophy, distal, with upper limb predominance
  • Distal hereditary motor neuropathy, type V

References

  1. Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ,Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, IonasescuV, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED. Glycyl tRNAsynthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinalmuscular atrophy type V. Am J Hum Genet. 2003 May;72(5):1293-9.
  2. Antonellis A, Lee-Lin SQ, Wasterlain A, Leo P, Quezado M, Goldfarb LG, MyungK, Burgess S, Fischbeck KH, Green ED. Functional analyses of glycyl-tRNAsynthetase mutations suggest a key role for tRNA-charging enzymes in peripheralaxons. J Neurosci. 2006 Oct 11;26(41):10397-406.
  3. Auer-Grumbach M, Löscher WN, Wagner K, Petek E, Körner E, Offenbacher H,Hartung HP. Phenotypic and genotypic heterogeneity in hereditary motorneuronopathy type V: a clinical, electrophysiological and genetic study. Brain.2000 Aug;123 ( Pt 8):1612-23.
  4. Beetz C, Pieber TR, Hertel N, Schabhüttl M, Fischer C, Trajanoski S, Graf E,Keiner S, Kurth I, Wieland T, Varga RE, Timmerman V, Reilly MM, Strom TM,Auer-Grumbach M. Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V. Am J Hum Genet. 2012 Jul 13;91(1):139-45.doi: 10.1016/j.ajhg.2012.05.007.
  5. Dubourg O, Azzedine H, Yaou RB, Pouget J, Barois A, Meininger V, Bouteiller D,Ruberg M, Brice A, LeGuern E. The G526R glycyl-tRNA synthetase gene mutation indistal hereditary motor neuropathy type V. Neurology. 2006 Jun 13;66(11):1721-6. Erratum in: Neurology. 2006 Aug 22;67(4):727.
  6. Irobi J, De Jonghe P, Timmerman V. Molecular genetics of distal hereditarymotor neuropathies. Hum Mol Genet. 2004 Oct 1;13 Spec No 2:R195-202. Review.
  7. Ito D, Suzuki N. Molecular pathogenesis of seipin/BSCL2-related motor neurondiseases. Ann Neurol. 2007 Mar;61(3):237-50.
  8. Ito D, Suzuki N. Seipinopathy: a novel endoplasmic reticulum stress-associateddisease. Brain. 2009 Jan;132(Pt 1):8-15. doi: 10.1093/brain/awn216.
  9. Rohkamm B, Reilly MM, Lochmüller H, Schlotter-Weigel B, Barisic N, Schöls L,Nicholson G, Pareyson D, Laurà M, Janecke AR, Miltenberger-Miltenyi G, John E,Fischer C, Grill F, Wakeling W, Davis M, Pieber TR, Auer-Grumbach M. Furtherevidence for genetic heterogeneity of distal HMN type V, CMT2 with predominanthand involvement and Silver syndrome. J Neurol Sci. 2007 Dec 15;263(1-2):100-6.
  10. Sivakumar K, Kyriakides T, Puls I, Nicholson GA, Funalot B, Antonellis A,Sambuughin N, Christodoulou K, Beggs JL, Zamba-Papanicolaou E, Ionasescu V,Dalakas MC, Green ED, Fischbeck KH, Goldfarb LG. Phenotypic spectrum of disordersassociated with glycyl-tRNA synthetase mutations. Brain. 2005 Oct;128(Pt10):2304-14.
  11. Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Hörl 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. Heterozygous missense mutations in BSCL2 are associated with distalhereditary motor neuropathy and Silver syndrome. Nat Genet. 2004 Mar;36(3):271-6.
More
©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Genetics & Heredity
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Peter Tang
View Times: 453
Entry Collection: MedlinePlus
Revision: 1 time (View History)
Update Date: 04 Jan 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback