HMSN6A
MCID: NRP066
MIFTS: 41

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 56
Peripheral Neuropathy and Optic Atrophy 56 58 73
Charcot-Marie-Tooth Disease Type 6 12 58 15
Hmsn Vi 58 73 54
Cmt6 56 58 73
Hereditary Motor and Sensory Neuropathy Type Vi 58 73
Hereditary Motor and Sensory Neuropathy Type 6 12 58
Hereditary Motor and Sensory Neuropathy Via 56 29
Hmsn Via 56 73
Hmsn6a 56 73
Hmsn6 56 73
Cmt6a 56 73
Neuropathy, Hereditary Motor and Sensory, Type Vi; Hmsn6 56
Neuropathy, Hereditary Motor and Sensory, Type Vi 56
Hereditary Motor and Sensory Neuropathy Type Via 73
Neuropathy, Hereditary Motor and Sensory, 6a 73
Charcot-Marie-Tooth Disease, Type 6a; Cmt6a 56
Hereditary Motor and Sensory Neuropathy Vi 13
Charcot-Marie-Tooth Disease, Type 6; Cmt6 56
Charcot-Marie-Tooth Disease, Type 6a 56
Charcot-Marie-Tooth Disease, Type 6 56
Charcot-Marie-Tooth Disease 6a 73
Charcot-Marie-Tooth Disease 6 73
Hmsn 6 58

Characteristics:

Orphanet epidemiological data:

58
hereditary motor and sensory neuropathy type 6
Inheritance: Autosomal dominant;

OMIM:

56
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:

31
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: 58  
Rare neurological diseases


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

UniProtKB/Swiss-Prot : 73 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 3-methylglutaconic aciduria, type iii and charcot-marie-tooth disease, x-linked dominant, 6. An important gene associated with Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy is MFN2 (Mitofusin 2), and among its related pathways/superpathways is rRNA processing in the mitochondrion. Affiliated tissues include brain, eye and b cells, 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 : 56 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...

Diseases in the Neuropathy, Hereditary Motor and Sensory, Type Via, with Optic Atrophy family:

Neuropathy, Hereditary Motor and Sensory, Type Vib, with Optic Atrophy Neuropathy, Hereditary Motor and Sensory, Type Vic, with Optic Atrophy

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

(show all 34)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria, type iii 29.0 TMEM126A SPG7 SLC25A46 OPA3 MFN2 C12orf65
2 charcot-marie-tooth disease, x-linked dominant, 6 12.2
3 achalasia-addisonianism-alacrima syndrome 11.3
4 neuropathy, hereditary motor and sensory, type vib, with optic atrophy 11.3
5 neuropathy, hereditary motor and sensory, type vic, with optic atrophy 11.3
6 sensory peripheral neuropathy 10.5
7 charcot-marie-tooth disease, demyelinating, type 1a 10.3
8 charcot-marie-tooth disease 10.3
9 tooth disease 10.3
10 axonal neuropathy 10.3
11 x-linked charcot-marie-tooth disease 10.3
12 charcot-marie-tooth disease, axonal, type 2b2 10.2 MFN2 C12orf65
13 3-methylglutaconic aciduria 10.2 TMEM126A OPA3
14 charcot-marie-tooth disease, axonal, type 2b1 10.2 MFN2 C12orf65
15 behr syndrome 10.2 OPA3 C12orf65
16 optic atrophy 1 10.2
17 yemenite deaf-blind hypopigmentation syndrome 10.2
18 muscular atrophy 10.2
19 tritanopia 10.1 TMEM126A OPA3
20 toxic optic neuropathy 10.0 TMEM126A OPA3 MFN2
21 myopathy 10.0
22 peripheral nervous system disease 10.0
23 mitochondrial myopathy 10.0
24 neuropathy 10.0
25 scotoma 10.0 TMEM126A OPA3
26 masa syndrome 9.7 SPG7 C12orf65
27 kearns-sayre syndrome 9.7 SPG7 OPA3 MFN2 C12orf65
28 cranial nerve disease 9.6 TMEM126A SPG7 OPA3 MFN2 C12orf65
29 optic nerve disease 9.6 TMEM126A SPG7 OPA3 MFN2 C12orf65
30 perrault syndrome 9.5 SPG7 MRPS34 MRPS16 MRPL44
31 sideroblastic anemia with b-cell immunodeficiency, periodic fevers, and developmental delay 9.4 TRMT5 TRMT10C
32 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.4 TRMT5 MRPL44 MRM2
33 leber optic atrophy 9.0 TMEM126A SPG7 OPA3 NSUN3 MRPS16 MFN2
34 mitochondrial metabolism disease 8.5 TRMT10C SPG7 SLC25A46 OPA3 MRPS34 MRPS16

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:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 mild neurosensory hearing impairment 31 occasional (7.5%) HP:0008587
2 scoliosis 31 HP:0002650
3 optic atrophy 31 HP:0000648
4 abnormality of visual evoked potentials 31 HP:0000649
5 areflexia 31 HP:0001284
6 pes cavus 31 HP:0001761
7 decreased motor nerve conduction velocity 31 HP:0003431
8 anosmia 31 HP:0000458
9 hyporeflexia 31 HP:0001265
10 central scotoma 31 HP:0000603
11 slow decrease in visual acuity 31 HP:0007924
12 optic disc pallor 31 HP:0000543
13 proximal muscle weakness 31 HP:0003701
14 tinnitus 31 HP:0000360
15 distal amyotrophy 31 HP:0003693
16 limb muscle weakness 31 HP:0003690
17 distal muscle weakness 31 HP:0002460
18 steppage gait 31 HP:0003376
19 vocal cord paresis 31 HP:0001604
20 lumbar hyperlordosis 31 HP:0002938
21 distal sensory impairment 31 HP:0002936
22 dysmetric saccades 31 HP:0000641
23 distal sensory impairment of all modalities 31 HP:0003409
24 positive romberg sign 31 HP:0002403
25 axonal degeneration/regeneration 31 HP:0003378
26 color vision defect 31 HP:0000551

Symptoms via clinical synopsis from OMIM:

56
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:

40
Brain, Eye, B Cells

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. 54 56 6
18946002 2008
2
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. 54 56 6
16437557 2006
3
Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. 54 6
16835246 2006
4
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. 6
15064763 2004
5
Hereditary motor and sensory neuropathy type VI with optic atrophy. 56
14516807 2003
6
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
7
Autosomal recessive inheritance of hereditary motor and sensory neuropathy with optic atrophy. 56
9120454 1997
8
Autosomal dominant optic atrophy with asymptomatic peripheral neuropathy. 56
8708653 1996
9
Genetic heterogeneity of hereditary motor and sensory neuropathy type VI. 56
8576556 1995
10
Charcot-Marie-Tooth disease with primary optic atrophy; report of a case. 56
13716305 1960
11
Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. 61
30250212 2018
12
Homozygosity mapping of Marinesco-Sjögren syndrome to 5q31. 61
14512967 2003
13
Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation. 61
11071149 2000
14
[A case of familial mitochondrial myopathy associated with peripheral neuropathy and optic atrophy]. 61
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 (show all 11) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MFN2 NM_014874.3(MFN2):c.2219G>C (p.Trp740Ser)SNV Pathogenic 2269 rs28940292 1:12071567-12071567 1:12011510-12011510
2 MFN2 NM_014874.3(MFN2):c.280C>T (p.Arg94Trp)SNV Pathogenic 2276 rs119103263 1:12052716-12052716 1:11992659-11992659
3 MFN2 NM_014874.3(MFN2):c.827A>G (p.Gln276Arg)SNV Pathogenic 2277 rs119103264 1:12061468-12061468 1:12001411-12001411
4 MFN2 NM_014874.3(MFN2):c.1090C>T (p.Arg364Trp)SNV Pathogenic 2278 rs119103265 1:12062090-12062090 1:12002033-12002033
5 MFN2 NM_014874.3(MFN2):c.310C>T (p.Arg104Trp)SNV Pathogenic 2281 rs119103268 1:12052746-12052746 1:11992689-11992689
6 MFN2 NM_014874.3(MFN2):c.2119C>T (p.Arg707Trp)SNV Pathogenic/Likely pathogenic 2280 rs119103267 1:12069698-12069698 1:12009641-12009641
7 MFN2 NM_014874.3(MFN2):c.1839dup (p.Thr614fs)duplication Likely pathogenic 488546 rs1553145402 1:12066715-12066716 1:12006658-12006659
8 MFN2 NM_014874.3(MFN2):c.1252C>T (p.Arg418Ter)SNV Likely pathogenic 372790 rs1057517987 1:12064140-12064140 1:12004083-12004083
9 MFN2 NM_001127660.1(MFN2):c.720C>G (p.Phe240Leu)SNV Likely pathogenic 437424 rs864622480 1:12059056-12059056 1:11998999-11998999
10 MFN2 NM_001127660.1(MFN2):c.617C>T (p.Thr206Ile)SNV Conflicting interpretations of pathogenicity 2279 rs119103266 1:12058844-12058844 1:11998787-11998787
11 MFN2 NM_014874.3(MFN2):c.1143_1145GGC[1] (p.Ala383del)short repeat Uncertain significance 446368 rs1553144065 1:12062143-12062145 1:12002086-12002088

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

73
# 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...

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
9.83 TRMT10C MRM2

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 mitochondrial inner membrane GO:0005743 9.55 TMEM126A SPG7 MRPS34 MRPS16 MRPL44
2 ribosome GO:0005840 9.54 MRPS34 MRPS16 MRPL44
3 mitochondrion GO:0005739 9.47 TRMT5 TRMT10C TMEM126A TEFM SPG7 SLC25A46
4 mitochondrial large ribosomal subunit GO:0005762 9.43 NSUN3 MRPL44 C12orf65
5 mitochondrial nucleoid GO:0042645 9.4 TRMT10C TEFM
6 mitochondrial matrix GO:0005759 9.35 TRMT5 TRMT10C TEFM NSUN3 MRM2
7 mitochondrial small ribosomal subunit GO:0005763 9.32 MRPS34 MRPS16

Biological processes 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 mitochondrial translational termination GO:0070126 9.43 MRPS34 MRPS16 MRPL44
2 mitochondrial translation GO:0032543 9.37 MRPS34 MRPS16
3 mitochondrial translational elongation GO:0070125 9.33 MRPS34 MRPS16 MRPL44
4 rRNA methylation GO:0031167 9.32 NSUN3 MRM2
5 methylation GO:0032259 9.26 TRMT5 TRMT10C NSUN3 MRM2
6 mitochondrial tRNA methylation GO:0070901 8.62 TRMT5 TRMT10C

Molecular functions 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 methyltransferase activity GO:0008168 9.26 TRMT5 TRMT10C NSUN3 MRM2
2 tRNA binding GO:0000049 9.16 TRMT10C NSUN3
3 tRNA (guanine-N1-)-methyltransferase activity GO:0009019 8.62 TRMT5 TRMT10C

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

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