HMSNO
MCID: NRP009
MIFTS: 33

Neuropathy, Hereditary Motor and Sensory, Okinawa Type (HMSNO)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

MalaCards integrated aliases for Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

Name: Neuropathy, Hereditary Motor and Sensory, Okinawa Type 57 20 72 70
Hereditary Motor and Sensory Neuropathy, Proximal Type 20 58 72 13
Hereditary Motor and Sensory Neuropathy, Okinawa Type 57 58 29 6
Hmsno 57 20 72
Hmsnp 20 58 72
Hereditary Motor and Sensory Neuropathy, Proximal Type, Formerly; Hmsnp, Formerly 57
Hereditary Motor and Sensory Neuropathy, Proximal Type, Formerly 57
Neuropathy, Motor and Sensory, Hereditary, Okinawa Type 39
Hereditary Motor and Sensory Neuropathy Okinawa 72
Hmsnp, Formerly 57

Characteristics:

Orphanet epidemiological data:

58

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
slow progression
adult onset (27 to 48 years)
some patients may become bedridden 10 to 20 years after onset
prevalent among individuals of east asian descent

Inheritance:
autosomal dominant


HPO:

31
neuropathy, hereditary motor and sensory, okinawa type:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 604484
MeSH 44 D015417
MESH via Orphanet 45 C535717
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 71 C1858338
Orphanet 58 ORPHA90117
MedGen 41 C1858338
UMLS 70 C1858338

Summaries for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 90117 Definition Hereditary motor and sensory neuropathy, Okinawa type is a rare, genetic, axonal hereditary motor and sensory neuropathy characterized by the adult-onset of slowly progressive, symmetric, proximal dominant muscle weakness and atrophy, painful muscle cramps, fasciculations and distal sensory impairment, mostly (but not exclusively) in individuals (and their descendents) from the Okinawa region in Japan. Absent deep tendon reflexes, elevated creatine kinase levels and autosomal dominant inheritance are also characteristic.

MalaCards based summary : Neuropathy, Hereditary Motor and Sensory, Okinawa Type, also known as hereditary motor and sensory neuropathy, proximal type, is related to neuropathy and charcot-marie-tooth disease, axonal, type 2e, and has symptoms including muscular fasciculation An important gene associated with Neuropathy, Hereditary Motor and Sensory, Okinawa Type is TFG (Trafficking From ER To Golgi Regulator). Affiliated tissues include spinal cord and dorsal root ganglion, and related phenotypes are hand tremor and areflexia

OMIM® : 57 HMSNO is an autosomal dominant neurodegenerative disorder characterized by young adult onset of proximal or distal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis (ALS; see 105400) (summary by Ishiura et al., 2012). (604484) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Neuropathy, hereditary motor and sensory, Okinawa type: A neurodegenerative disorder characterized by young adult onset of proximal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis.

Related Diseases for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Diseases related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neuropathy 30.8 TFG HMSNO
2 charcot-marie-tooth disease, axonal, type 2e 11.5

Symptoms & Phenotypes for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Human phenotypes related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

31 58 (show all 43)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hand tremor 31 occasional (7.5%) HP:0002378
2 areflexia 58 31 Very frequent (99-80%) HP:0001284
3 distal sensory impairment 58 31 Frequent (79-30%) HP:0002936
4 gait disturbance 31 HP:0001288
5 tremor 58 Frequent (79-30%)
6 dysphagia 58 Occasional (29-5%)
7 tetraplegia 31 HP:0002445
8 elevated serum creatine kinase 58 Frequent (79-30%)
9 bulbar signs 58 Frequent (79-30%)
10 dyspnea 58 Occasional (29-5%)
11 hyperlipidemia 31 HP:0003077
12 cough 58 Very frequent (99-80%)
13 abnormality of the urinary system 58 Frequent (79-30%)
14 sensory neuropathy 31 HP:0000763
15 peripheral neuropathy 31 HP:0009830
16 fasciculations 31 HP:0002380
17 respiratory failure 58 Occasional (29-5%)
18 proximal amyotrophy 31 HP:0007126
19 respiratory failure requiring assisted ventilation 58 Occasional (29-5%)
20 mildly elevated creatine kinase 31 HP:0008180
21 sensory impairment 58 Very frequent (99-80%)
22 aspiration pneumonia 58 Occasional (29-5%)
23 proximal muscle weakness 31 HP:0003701
24 inability to walk 58 Frequent (79-30%)
25 upper limb muscle weakness 58 Very frequent (99-80%)
26 intermittent painful muscle spasms 58 Very frequent (99-80%)
27 degeneration of anterior horn cells 31 HP:0002398
28 muscle spasm 31 HP:0003394
29 limb fasciculations 58 Frequent (79-30%)
30 gliosis 31 HP:0002171
31 lower limb muscle weakness 58 Very frequent (99-80%)
32 emg: positive sharp waves 58 Frequent (79-30%)
33 difficulty standing 58 Frequent (79-30%)
34 decreased number of peripheral myelinated nerve fibers 31 HP:0003380
35 muscle fibrillation 58 Frequent (79-30%)
36 fatiguable weakness of proximal limb muscles 58 Very frequent (99-80%)
37 axonal degeneration 31 HP:0040078
38 nasogastric tube feeding in infancy 58 Occasional (29-5%)
39 abnormal cranial nerve physiology 58 Frequent (79-30%)
40 abnormal peripheral action potential amplitude 58 Very frequent (99-80%)
41 abnormality of the seventh cranial nerve 58 Occasional (29-5%)
42 abnormal glucose homeostasis 58 Occasional (29-5%)
43 lower cranial nerve dysfunction 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
gait disturbance
gliosis
loss of anterior horn cells
bulbar symptoms may occur (less common)
hand tremor (in some patients)
more
Muscle Soft Tissue:
fasciculations
muscle weakness and atrophy, proximal
muscle weakness and atrophy, distal
painful muscle cramps
neurogenic changes seen on emg and biopsy
more
Laboratory Abnormalities:
hyperlipidemia
mildly increased serum creatine kinase

Neurologic Peripheral Nervous System:
distal sensory loss
hypo- or areflexia
loss of myelinated fibers
axonal motor and sensory neuropathy
mild loss of touch and temperature
more

Clinical features from OMIM®:

604484 (Updated 20-May-2021)

UMLS symptoms related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type:


muscular fasciculation

Drugs & Therapeutics for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Search Clinical Trials , NIH Clinical Center for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Genetic Tests for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Genetic tests related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

# Genetic test Affiliating Genes
1 Hereditary Motor and Sensory Neuropathy, Okinawa Type 29 TFG

Anatomical Context for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

MalaCards organs/tissues related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

40
Spinal Cord, Dorsal Root Ganglion

Publications for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Articles related to Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

(show all 18)
# Title Authors PMID Year
1
A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. 57 6
25098539 2014
2
Proximal dominant hereditary motor and sensory neuropathy with proximal dominance association with mutation in the TRK-fused gene. 57 6
23553329 2013
3
The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement. 57 6
22883144 2012
4
Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation. 6
30157421 2018
5
R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome. 6
29971521 2018
6
Proteasome impairment in neural cells derived from HMSN-P patient iPSCs. 6
28196470 2017
7
Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia. 6
27492651 2016
8
Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy. 6
26257172 2015
9
HMSN-P caused by p.Pro285Leu mutation in TFG is not confined to patients with Far East ancestry. 6
25725944 2015
10
Evidence of TRK-Fused Gene (TFG1) function in the ubiquitin-proteasome system. 6
24613659 2014
11
Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure. 6
23479643 2013
12
Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy. 57
21836032 2011
13
Autosomal dominant HMSN with proximal involvement: new Brazilian cases. 57
19838524 2009
14
Hereditary motor and sensory neuropathy (proximal dominant form, HMSN-P) among Brazilians of Japanese ancestry. 57
17764830 2007
15
Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity. 57
17906970 2007
16
Gene for hereditary motor and sensory neuropathy (proximal dominant form) mapped to 3q13.1. 57
10545038 1999
17
A new type of hereditary motor and sensory neuropathy linked to chromosome 3. 57
9189038 1997
18
[History of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P)]. 61
24291927 2013

Variations for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

ClinVar genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

6 (show top 50) (show all 105)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TFG NM_006070.6(TFG):c.854C>T (p.Pro285Leu) SNV Pathogenic 37089 rs207482230 GRCh37: 3:100467026-100467026
GRCh38: 3:100748182-100748182
2 TFG NM_006070.6(TFG):c.316C>T (p.Arg106Cys) SNV Pathogenic 100909 rs587777175 GRCh37: 3:100447603-100447603
GRCh38: 3:100728759-100728759
3 TFG NM_006070.6(TFG):c.854C>T (p.Pro285Leu) SNV Pathogenic 37089 rs207482230 GRCh37: 3:100467026-100467026
GRCh38: 3:100748182-100748182
4 TFG NM_006070.6(TFG):c.806G>T (p.Gly269Val) SNV Pathogenic 156445 rs587777789 GRCh37: 3:100463761-100463761
GRCh38: 3:100744917-100744917
5 TFG NM_006070.6(TFG):c.68G>A (p.Arg23Gln) SNV Uncertain significance 579063 rs774808090 GRCh37: 3:100432597-100432597
GRCh38: 3:100713753-100713753
6 TFG NM_006070.6(TFG):c.286C>T (p.Pro96Ser) SNV Uncertain significance 835424 GRCh37: 3:100447573-100447573
GRCh38: 3:100728729-100728729
7 TFG NM_006070.6(TFG):c.464A>G (p.Lys155Arg) SNV Uncertain significance 839794 GRCh37: 3:100451400-100451400
GRCh38: 3:100732556-100732556
8 TFG NM_006070.6(TFG):c.467A>G (p.Gln156Arg) SNV Uncertain significance 849769 GRCh37: 3:100451403-100451403
GRCh38: 3:100732559-100732559
9 TFG NM_006070.6(TFG):c.268G>A (p.Val90Ile) SNV Uncertain significance 851188 GRCh37: 3:100438902-100438902
GRCh38: 3:100720058-100720058
10 TFG NM_006070.6(TFG):c.1154G>A (p.Arg385His) SNV Uncertain significance 851831 GRCh37: 3:100467326-100467326
GRCh38: 3:100748482-100748482
11 TFG NM_006070.6(TFG):c.1133C>T (p.Pro378Leu) SNV Uncertain significance 852670 GRCh37: 3:100467305-100467305
GRCh38: 3:100748461-100748461
12 TFG NM_006070.6(TFG):c.664G>A (p.Val222Ile) SNV Uncertain significance 855052 GRCh37: 3:100455503-100455503
GRCh38: 3:100736659-100736659
13 TFG NM_006070.6(TFG):c.484G>A (p.Ala162Thr) SNV Uncertain significance 858796 GRCh37: 3:100451420-100451420
GRCh38: 3:100732576-100732576
14 TFG NM_006070.6(TFG):c.544A>C (p.Met182Leu) SNV Uncertain significance 859182 GRCh37: 3:100451480-100451480
GRCh38: 3:100732636-100732636
15 TFG NM_006070.6(TFG):c.898C>A (p.Pro300Thr) SNV Uncertain significance 859556 GRCh37: 3:100467070-100467070
GRCh38: 3:100748226-100748226
16 TFG NM_006070.6(TFG):c.1153C>T (p.Arg385Cys) SNV Uncertain significance 862024 GRCh37: 3:100467325-100467325
GRCh38: 3:100748481-100748481
17 TFG NM_006070.6(TFG):c.395C>A (p.Ser132Tyr) SNV Uncertain significance 864373 GRCh37: 3:100447682-100447682
GRCh38: 3:100728838-100728838
18 TFG NM_006070.6(TFG):c.567T>A (p.Asp189Glu) SNV Uncertain significance 864470 GRCh37: 3:100451503-100451503
GRCh38: 3:100732659-100732659
19 TFG NM_006070.6(TFG):c.1199G>C (p.Arg400Pro) SNV Uncertain significance 936897 GRCh37: 3:100467371-100467371
GRCh38: 3:100748527-100748527
20 TFG NM_006070.6(TFG):c.1172G>T (p.Gly391Val) SNV Uncertain significance 941860 GRCh37: 3:100467344-100467344
GRCh38: 3:100748500-100748500
21 TFG NM_006070.6(TFG):c.97T>C (p.Tyr33His) SNV Uncertain significance 941987 GRCh37: 3:100432626-100432626
GRCh38: 3:100713782-100713782
22 TFG NM_006070.6(TFG):c.976G>T (p.Ala326Ser) SNV Uncertain significance 946901 GRCh37: 3:100467148-100467148
GRCh38: 3:100748304-100748304
23 TFG NM_006070.6(TFG):c.608G>A (p.Arg203His) SNV Uncertain significance 951265 GRCh37: 3:100455447-100455447
GRCh38: 3:100736603-100736603
24 TFG NM_006070.6(TFG):c.196A>G (p.Ile66Val) SNV Uncertain significance 952320 GRCh37: 3:100438830-100438830
GRCh38: 3:100719986-100719986
25 TFG NM_006070.6(TFG):c.409G>C (p.Glu137Gln) SNV Uncertain significance 953420 GRCh37: 3:100447696-100447696
GRCh38: 3:100728852-100728852
26 TFG NM_006070.6(TFG):c.1087T>G (p.Phe363Val) SNV Uncertain significance 960261 GRCh37: 3:100467259-100467259
GRCh38: 3:100748415-100748415
27 TFG NM_006070.6(TFG):c.870A>G (p.Gly290=) SNV Uncertain significance 963189 GRCh37: 3:100467042-100467042
GRCh38: 3:100748198-100748198
28 TFG NM_006070.6(TFG):c.256C>G (p.Leu86Val) SNV Uncertain significance 964397 GRCh37: 3:100438890-100438890
GRCh38: 3:100720046-100720046
29 TFG NM_006070.6(TFG):c.580+6T>C SNV Uncertain significance 998737 GRCh37: 3:100451522-100451522
GRCh38: 3:100732678-100732678
30 TFG NC_000003.11:g.(?_100463667)_(100467385_?)dup Duplication Uncertain significance 999903 GRCh37: 3:100463667-100467385
GRCh38:
31 TFG NM_006070.6(TFG):c.373C>T (p.Pro125Ser) SNV Uncertain significance 1003573 GRCh37: 3:100447660-100447660
GRCh38: 3:100728816-100728816
32 TFG NM_006070.6(TFG):c.198A>G (p.Ile66Met) SNV Uncertain significance 1004051 GRCh37: 3:100438832-100438832
GRCh38: 3:100719988-100719988
33 TFG NM_006070.6(TFG):c.9_10delinsGA (p.Gln4Lys) Indel Uncertain significance 1009525 GRCh37: 3:100432538-100432539
GRCh38: 3:100713694-100713695
34 TFG NM_006070.6(TFG):c.353G>A (p.Arg118His) SNV Uncertain significance 1011451 GRCh37: 3:100447640-100447640
GRCh38: 3:100728796-100728796
35 TFG NM_006070.6(TFG):c.986dup (p.Tyr329Ter) Duplication Uncertain significance 1019608 GRCh37: 3:100467157-100467158
GRCh38: 3:100748313-100748314
36 TFG NM_006070.6(TFG):c.820+3G>A SNV Uncertain significance 1019766 GRCh37: 3:100463778-100463778
GRCh38: 3:100744934-100744934
37 TFG NM_006070.6(TFG):c.850C>G (p.Gln284Glu) SNV Uncertain significance 1025286 GRCh37: 3:100467022-100467022
GRCh38: 3:100748178-100748178
38 TFG NM_006070.6(TFG):c.61A>T (p.Ile21Phe) SNV Uncertain significance 1035040 GRCh37: 3:100432590-100432590
GRCh38: 3:100713746-100713746
39 TFG NM_006070.6(TFG):c.269-5T>C SNV Uncertain significance 1037656 GRCh37: 3:100447551-100447551
GRCh38: 3:100728707-100728707
40 TFG NM_006070.6(TFG):c.738G>C (p.Gln246His) SNV Uncertain significance 1039628 GRCh37: 3:100463693-100463693
GRCh38: 3:100744849-100744849
41 TFG NM_006070.6(TFG):c.1163T>G (p.Phe388Cys) SNV Uncertain significance 1051770 GRCh37: 3:100467335-100467335
GRCh38: 3:100748491-100748491
42 TFG NM_006070.6(TFG):c.622G>A (p.Asp208Asn) SNV Uncertain significance 1052695 GRCh37: 3:100455461-100455461
GRCh38: 3:100736617-100736617
43 TFG NM_006070.6(TFG):c.34A>G (p.Ile12Val) SNV Uncertain significance 1054786 GRCh37: 3:100432563-100432563
GRCh38: 3:100713719-100713719
44 TFG NC_000003.11:g.(?_100455410)_(100463785_?)del Deletion Uncertain significance 1062624 GRCh37: 3:100455410-100463785
GRCh38:
45 TFG NM_006070.6(TFG):c.499G>A (p.Ala167Thr) SNV Uncertain significance 1063471 GRCh37: 3:100451435-100451435
GRCh38: 3:100732591-100732591
46 TFG NM_006070.6(TFG):c.1157C>T (p.Pro386Leu) SNV Uncertain significance 534745 rs766049461 GRCh37: 3:100467329-100467329
GRCh38: 3:100748485-100748485
47 TFG NM_006070.6(TFG):c.943C>T (p.Pro315Ser) SNV Uncertain significance 534746 rs1553704852 GRCh37: 3:100467115-100467115
GRCh38: 3:100748271-100748271
48 TFG NM_006070.6(TFG):c.309A>G (p.Lys103=) SNV Uncertain significance 534747 rs369508900 GRCh37: 3:100447596-100447596
GRCh38: 3:100728752-100728752
49 TFG NM_006070.6(TFG):c.1006C>T (p.Pro336Ser) SNV Uncertain significance 234835 rs371681149 GRCh37: 3:100467178-100467178
GRCh38: 3:100748334-100748334
50 TFG NM_006070.6(TFG):c.716T>C (p.Ile239Thr) SNV Uncertain significance 568023 rs146004809 GRCh37: 3:100455555-100455555
GRCh38: 3:100736711-100736711

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Okinawa Type:

72
# Symbol AA change Variation ID SNP ID
1 TFG p.Pro285Leu VAR_068917 rs207482230

Expression for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Search GEO for disease gene expression data for Neuropathy, Hereditary Motor and Sensory, Okinawa Type.

Pathways for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

GO Terms for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

Sources for Neuropathy, Hereditary Motor and Sensory, Okinawa Type

3 CDC
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45 MESH via Orphanet
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56 OMIM via Orphanet
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