HMSN6A
MCID: NRP066
MIFTS: 35

Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy (HMSN6A)

Categories: Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

MalaCards integrated aliases for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

Name: Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy 57
Peripheral Neuropathy and Optic Atrophy 57 59 74
Charcot-Marie-Tooth Disease Type 6 12 59 15
Hmsn Vi 59 74 55
Cmt6 57 59 74
Hereditary Motor and Sensory Neuropathy Type Vi 59 74
Hereditary Motor and Sensory Neuropathy Type 6 12 59
Hereditary Motor and Sensory Neuropathy Via 57 29
Hmsn Via 57 74
Hmsn6a 57 74
Hmsn6 57 74
Cmt6a 57 74
Neuropathy, Hereditary Motor and Sensory, Type Vi; Hmsn6 57
Neuropathy, Hereditary Motor and Sensory, Type Vi 57
Hereditary Motor and Sensory Neuropathy Type Via 74
Neuropathy, Hereditary Motor and Sensory, 6a 74
Charcot-Marie-Tooth Disease, Type 6a; Cmt6a 57
Hereditary Motor and Sensory Neuropathy Vi 13
Charcot-Marie-Tooth Disease, Type 6; Cmt6 57
Charcot-Marie-Tooth Disease, Type 6a 57
Charcot-Marie-Tooth Disease, Type 6 57
Charcot-Marie-Tooth Disease 6a 74
Charcot-Marie-Tooth Disease 6 74
Hmsn 6 59

Characteristics:

Orphanet epidemiological data:

59
hereditary motor and sensory neuropathy type 6
Inheritance: Autosomal dominant;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
early onset of peripheral neuropathy (mean 2.1 years, range 1 to 10 years)
later onset of optic atrophy (mean 19 years, range 5 to 50 years)
incomplete penetrance of optic atrophy
allelic disorder to charcot-marie-tooth disease type 2a2 (cmt2a2, )
autosomal recessive inheritance has also been reported


HPO:

32
neuropathy, hereditary motor and sensory, type via, with optic atrophy:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0080068
ICD10 via Orphanet 34 G60.0
UMLS via Orphanet 73 C0393807
Orphanet 59 ORPHA90120
MedGen 42 C0393807

Summaries for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

UniProtKB/Swiss-Prot : 74 Neuropathy, hereditary motor and sensory, 6A: An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.

MalaCards based summary : Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy, also known as peripheral neuropathy and optic atrophy, is related to neuropathy and 3-methylglutaconic aciduria, type iii. An important gene associated with Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy is MFN2 (Mitofusin 2). Affiliated tissues include brain, and related phenotypes are mild neurosensory hearing impairment and scoliosis

Disease Ontology : 12 A Charcot-Marie-Tooth disease that is characterized by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity.

OMIM : 57 Hereditary motor and sensory neuropathy type VI is an autosomal dominant neurologic disorder characterized by peripheral neuropathy and optic atrophy (summary by Voo et al., 2003). (601152)

Related Diseases for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Graphical network of the top 20 diseases related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:



Diseases related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy

Symptoms & Phenotypes for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Human phenotypes related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

32 (show all 26)
# Description HPO Frequency HPO Source Accession
1 mild neurosensory hearing impairment 32 occasional (7.5%) HP:0008587
2 scoliosis 32 HP:0002650
3 optic atrophy 32 HP:0000648
4 abnormality of visual evoked potentials 32 HP:0000649
5 areflexia 32 HP:0001284
6 pes cavus 32 HP:0001761
7 decreased motor nerve conduction velocity 32 HP:0003431
8 anosmia 32 HP:0000458
9 central scotoma 32 HP:0000603
10 hyporeflexia 32 HP:0001265
11 slow decrease in visual acuity 32 HP:0007924
12 optic disc pallor 32 HP:0000543
13 proximal muscle weakness 32 HP:0003701
14 tinnitus 32 HP:0000360
15 distal amyotrophy 32 HP:0003693
16 limb muscle weakness 32 HP:0003690
17 distal muscle weakness 32 HP:0002460
18 steppage gait 32 HP:0003376
19 vocal cord paresis 32 HP:0001604
20 lumbar hyperlordosis 32 HP:0002938
21 distal sensory impairment 32 HP:0002936
22 dysmetric saccades 32 HP:0000641
23 distal sensory impairment of all modalities 32 HP:0003409
24 positive romberg sign 32 HP:0002403
25 axonal degeneration/regeneration 32 HP:0003378
26 color vision defect 32 HP:0000551

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
optic atrophy
central scotoma
dysmetric saccades
pale optic disks
subacute deterioration of visual acuity
more
Skeletal Feet:
pes cavus

Head And Neck Ears:
hearing loss, mild (rare)
tinnitus (rare)

Respiratory Larynx:
vocal cord paresis in severe cases

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
proximal muscle weakness
distal sensory impairment of all modalities
positive romberg sign
more
Skeletal Spine:
lumbar hyperlordosis
scoliosis in severe cases

Head And Neck Nose:
anosmia (rare)

Clinical features from OMIM:

601152

Drugs & Therapeutics for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Search Clinical Trials , NIH Clinical Center for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy

Genetic Tests for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Genetic tests related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

# Genetic test Affiliating Genes
1 Hereditary Motor and Sensory Neuropathy Via 29

Anatomical Context for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

MalaCards organs/tissues related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

41
Brain

Publications for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Articles related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

(show all 14)
# Title Authors PMID Year
1
Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction. 9 8 71
18946002 2008
2
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. 9 8 71
16437557 2006
3
Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. 9 71
16835246 2006
4
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. 71
15064763 2004
5
Hereditary motor and sensory neuropathy type VI with optic atrophy. 8
14516807 2003
6
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 71
20301532 1998
7
Autosomal recessive inheritance of hereditary motor and sensory neuropathy with optic atrophy. 8
9120454 1997
8
Autosomal dominant optic atrophy with asymptomatic peripheral neuropathy. 8
8708653 1996
9
Genetic heterogeneity of hereditary motor and sensory neuropathy type VI. 8
8576556 1995
10
Charcot-Marie-Tooth disease with primary optic atrophy; report of a case. 8
13716305 1960
11
Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. 38
30250212 2018
12
Homozygosity mapping of Marinesco-Sjögren syndrome to 5q31. 38
14512967 2003
13
Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation. 38
11071149 2000
14
[A case of familial mitochondrial myopathy associated with peripheral neuropathy and optic atrophy]. 38
2831006 1987

Variations for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

ClinVar genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 MFN2 NM_014874.3(MFN2): c.280C> T (p.Arg94Trp) single nucleotide variant Pathogenic rs119103263 1:12052716-12052716 1:11992659-11992659
2 MFN2 NM_014874.3(MFN2): c.827A> G (p.Gln276Arg) single nucleotide variant Pathogenic rs119103264 1:12061468-12061468 1:12001411-12001411
3 MFN2 NM_014874.3(MFN2): c.1090C> T (p.Arg364Trp) single nucleotide variant Pathogenic rs119103265 1:12062090-12062090 1:12002033-12002033
4 MFN2 NM_014874.3(MFN2): c.617C> T (p.Thr206Ile) single nucleotide variant Pathogenic rs119103266 1:12058844-12058844 1:11998787-11998787
5 MFN2 NM_014874.3(MFN2): c.310C> T (p.Arg104Trp) single nucleotide variant Pathogenic rs119103268 1:12052746-12052746 1:11992689-11992689
6 MFN2 NM_014874.3(MFN2): c.2219G> C (p.Trp740Ser) single nucleotide variant Pathogenic rs28940292 1:12071567-12071567 1:12011510-12011510
7 MFN2 NM_014874.3(MFN2): c.2119C> T (p.Arg707Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119103267 1:12069698-12069698 1:12009641-12009641
8 MFN2 NM_014874.3(MFN2): c.720C> G (p.Phe240Leu) single nucleotide variant Likely pathogenic rs864622480 1:12059056-12059056 1:11998999-11998999
9 MFN2 NM_014874.3(MFN2): c.1839dup (p.Thr614fs) duplication Likely pathogenic rs1553145402 1:12066716-12066716 1:12006658-12006659
10 MFN2 NM_014874.3(MFN2): c.1143_1145GGC[1] (p.Ala383del) short repeat Uncertain significance rs1553144065 1:12062143-12062145 1:12002086-12002088

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy:

74
# Symbol AA change Variation ID SNP ID
1 MFN2 p.Arg94Gln VAR_018609 rs28940291
2 MFN2 p.Arg94Trp VAR_029876 rs119103263
3 MFN2 p.Thr206Ile VAR_029877 rs119103266
4 MFN2 p.Gln276Arg VAR_029878 rs119103264
5 MFN2 p.His361Tyr VAR_029879
6 MFN2 p.Arg364Trp VAR_029880 rs119103265

Expression for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Search GEO for disease gene expression data for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy.

Pathways for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

GO Terms for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

Cellular components related to Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.13 SLC25A46 MFN2 C12orf65
2 mitochondrial outer membrane GO:0005741 8.62 SLC25A46 MFN2

Sources for Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic...

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