HMSN6B
MCID: NRP043
MIFTS: 28

Neuropathy, Hereditary Motor and Sensory, Type Vib (HMSN6B)

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

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

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

Name: Neuropathy, Hereditary Motor and Sensory, Type Vib 58 76 30 6 17
Hmsn Vib 58 76
Hmsn6b 58 76
Cmt6b 58 76
Neuropathy, Motor and Sensory, Hereditary, Type Vib 41
Hereditary Motor and Sensory Neuropathy Type Vib 76
Neuropathy, Hereditary Motor and Sensory, 6b 76
Charcot-Marie-Tooth Disease, Type 6b; Cmt6b 58
Charcot-Marie-Tooth Disease, Type 6b 58
Charcot-Marie-Tooth Disease 6b 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
highly variable severity
onset of optic atrophy in first decade
onset of peripheral neuropathy ranges from childhood to mid-adulthood
the most severely affected patients may die in infancy


HPO:

33
neuropathy, hereditary motor and sensory, type vib:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Neuropathy, Hereditary Motor and Sensory, Type Vib

UniProtKB/Swiss-Prot : 76 Neuropathy, hereditary motor and sensory, 6B: An autosomal recessive neurologic disorder characterized by early- onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. 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 Vib, is also known as hmsn vib. An important gene associated with Neuropathy, Hereditary Motor and Sensory, Type Vib is SLC25A46 (Solute Carrier Family 25 Member 46). Affiliated tissues include brain, cerebellum and eye, and related phenotypes are ataxia and hyperreflexia

OMIM : 58 Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they may show abnormal movements, such as ataxia, dysmetria, and myoclonus. The most severely affected patients are hypotonic at birth and die in infancy (summary by Abrams et al., 2015 and Wan et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of HMSN6, see HMSN6A (601152). (616505)

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

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

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

33 (show all 26)
# Description HPO Frequency HPO Source Accession
1 ataxia 33 occasional (7.5%) HP:0001251
2 hyperreflexia 33 occasional (7.5%) HP:0001347
3 babinski sign 33 occasional (7.5%) HP:0003487
4 cerebellar atrophy 33 occasional (7.5%) HP:0001272
5 nystagmus 33 HP:0000639
6 muscle weakness 33 HP:0001324
7 tremor 33 HP:0001337
8 narrow palate 33 HP:0000189
9 global developmental delay 33 HP:0001263
10 anteverted nares 33 HP:0000463
11 optic atrophy 33 HP:0000648
12 flexion contracture 33 HP:0001371
13 progressive visual loss 33 HP:0000529
14 myoclonus 33 HP:0001336
15 inverted nipples 33 HP:0003186
16 dysmetria 33 HP:0001310
17 pes cavus 33 HP:0001761
18 bulbous nose 33 HP:0000414
19 hyporeflexia 33 HP:0001265
20 tented upper lip vermilion 33 HP:0010804
21 tapered finger 33 HP:0001182
22 generalized hypotonia 33 HP:0001290
23 steppage gait 33 HP:0003376
24 distal sensory impairment 33 HP:0002936
25 exotropia 33 HP:0000577
26 narrow forehead 33 HP:0000341

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
optic atrophy
exotropia
progressive visual impairment
rod-cone dysfunction

Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
hyporeflexia
distal sensory impairment
sensorimotor axonal neuropathy

Respiratory:
respiratory failure (in some patients)

Head And Neck Ears:
abnormal ears (patient a)

Head And Neck Mouth:
tented upper lip (patient a)
narrow palate (patient a)

Skeletal:
contractures (patient a)

Neurologic Central Nervous System:
ataxia
tremor
myoclonus
dysmetria
cerebellar atrophy
more
Skeletal Feet:
pes cavus

Muscle Soft Tissue:
hypotonia
distal muscle atrophy, lower legs
distal muscle weakness, lower legs

Head And Neck Head:
bitemporal narrowing (patient a)

Head And Neck Nose:
upturned nose (patient a)
bulbous nasal tip (patient a)

Chest Breasts:
inverted nipples (patient a)

Skeletal Hands:
tapered fingers (patient a)

Clinical features from OMIM:

616505

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

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

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

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

# Genetic test Affiliating Genes
1 Neuropathy, Hereditary Motor and Sensory, Type Vib 30 SLC25A46

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

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

42
Brain, Cerebellum, Eye

Publications for Neuropathy, Hereditary Motor and Sensory, Type Vib

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

# Title Authors Year
1
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. ( 27390132 )
2016
2
Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. ( 27543974 )
2016
3
SLC25A46 mutations underlie progressive myoclonic ataxia with optic atrophy and neuropathy. ( 27430653 )
2016
4
Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. ( 26168012 )
2015

Variations for Neuropathy, Hereditary Motor and Sensory, Type Vib

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

76
# Symbol AA change Variation ID SNP ID
1 SLC25A46 p.Gly249Asp VAR_075818 rs200725073
2 SLC25A46 p.Pro333Leu VAR_075819 rs105751875
3 SLC25A46 p.Glu335Asp VAR_075820 rs105751874
4 SLC25A46 p.Arg340Cys VAR_075821 rs746681765

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

6 (show top 50) (show all 109)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A46 NM_138773.3(SLC25A46): c.166dupC (p.His56Profs) duplication Pathogenic rs1057519416 GRCh38 Chromosome 5, 110739285: 110739285
2 SLC25A46 NM_138773.3(SLC25A46): c.166dupC (p.His56Profs) duplication Pathogenic rs1057519416 GRCh37 Chromosome 5, 110074986: 110074986
3 SLC25A46 NM_138773.3(SLC25A46): c.746G> A (p.Gly249Asp) single nucleotide variant Pathogenic rs200725073 GRCh38 Chromosome 5, 110761271: 110761271
4 SLC25A46 NM_138773.3(SLC25A46): c.746G> A (p.Gly249Asp) single nucleotide variant Pathogenic rs200725073 GRCh37 Chromosome 5, 110096971: 110096971
5 SLC25A46 NM_138773.3(SLC25A46): c.1005A> T (p.Glu335Asp) single nucleotide variant Pathogenic rs1057518748 GRCh37 Chromosome 5, 110097230: 110097230
6 SLC25A46 NM_138773.3(SLC25A46): c.1005A> T (p.Glu335Asp) single nucleotide variant Pathogenic rs1057518748 GRCh38 Chromosome 5, 110761530: 110761530
7 SLC25A46 NM_138773.3(SLC25A46): c.882_885dup (p.Asn296Leufs) duplication Pathogenic rs1057518749 GRCh38 Chromosome 5, 110761407: 110761410
8 SLC25A46 NM_138773.3(SLC25A46): c.882_885dup (p.Asn296Leufs) duplication Pathogenic rs1057518749 GRCh37 Chromosome 5, 110097107: 110097110
9 SLC25A46 NM_138773.3(SLC25A46): c.998C> T (p.Pro333Leu) single nucleotide variant Pathogenic rs1057518750 GRCh37 Chromosome 5, 110097223: 110097223
10 SLC25A46 NM_138773.3(SLC25A46): c.998C> T (p.Pro333Leu) single nucleotide variant Pathogenic rs1057518750 GRCh38 Chromosome 5, 110761523: 110761523
11 SLC25A46 NM_138773.3(SLC25A46): c.1018C> T (p.Arg340Cys) single nucleotide variant Pathogenic rs746681765 GRCh38 Chromosome 5, 110761543: 110761543
12 SLC25A46 NM_138773.3(SLC25A46): c.1018C> T (p.Arg340Cys) single nucleotide variant Pathogenic rs746681765 GRCh37 Chromosome 5, 110097243: 110097243
13 SLC25A46 SCL25A46, 1.897-KB DEL deletion Pathogenic
14 SLC25A46 NM_138773.3(SLC25A46): c.1022T> C (p.Leu341Pro) single nucleotide variant Pathogenic rs1057519294 GRCh38 Chromosome 5, 110761547: 110761547
15 SLC25A46 NM_138773.3(SLC25A46): c.1022T> C (p.Leu341Pro) single nucleotide variant Pathogenic rs1057519294 GRCh37 Chromosome 5, 110097247: 110097247
16 SLC25A46 NM_138773.3(SLC25A46): c.413T> G (p.Leu138Arg) single nucleotide variant Pathogenic rs1057519295 GRCh37 Chromosome 5, 110081998: 110081998
17 SLC25A46 NM_138773.3(SLC25A46): c.413T> G (p.Leu138Arg) single nucleotide variant Pathogenic rs1057519295 GRCh38 Chromosome 5, 110746297: 110746297
18 SLC25A46 NM_138773.3(SLC25A46): c.425C> T (p.Thr142Ile) single nucleotide variant Pathogenic rs1057519296 GRCh37 Chromosome 5, 110082010: 110082010
19 SLC25A46 NM_138773.3(SLC25A46): c.425C> T (p.Thr142Ile) single nucleotide variant Pathogenic rs1057519296 GRCh38 Chromosome 5, 110746309: 110746309
20 SLC25A46 NM_138773.2(SLC25A46): c.803C> T (p.Thr268Met) single nucleotide variant Conflicting interpretations of pathogenicity rs751900293 GRCh38 Chromosome 5, 110761328: 110761328
21 SLC25A46 NM_138773.2(SLC25A46): c.803C> T (p.Thr268Met) single nucleotide variant Conflicting interpretations of pathogenicity rs751900293 GRCh37 Chromosome 5, 110097028: 110097028
22 SLC25A46 NM_138773.3(SLC25A46): c.196G> T (p.Val66Leu) single nucleotide variant Uncertain significance rs758140632 GRCh38 Chromosome 5, 110739315: 110739315
23 SLC25A46 NM_138773.3(SLC25A46): c.196G> T (p.Val66Leu) single nucleotide variant Uncertain significance rs758140632 GRCh37 Chromosome 5, 110075016: 110075016
24 SLC25A46 NM_138773.3(SLC25A46): c.385-4A> G single nucleotide variant Likely benign rs377289513 GRCh38 Chromosome 5, 110746265: 110746265
25 SLC25A46 NM_138773.3(SLC25A46): c.385-4A> G single nucleotide variant Likely benign rs377289513 GRCh37 Chromosome 5, 110081966: 110081966
26 SLC25A46 NM_138773.3(SLC25A46): c.429C> T (p.Val143=) single nucleotide variant Benign rs35220834 GRCh38 Chromosome 5, 110746313: 110746313
27 SLC25A46 NM_138773.3(SLC25A46): c.429C> T (p.Val143=) single nucleotide variant Benign rs35220834 GRCh37 Chromosome 5, 110082014: 110082014
28 SLC25A46 NM_138773.3(SLC25A46): c.630C> T (p.Tyr210=) single nucleotide variant Benign rs201039547 GRCh38 Chromosome 5, 110756711: 110756711
29 SLC25A46 NM_138773.3(SLC25A46): c.630C> T (p.Tyr210=) single nucleotide variant Benign rs201039547 GRCh37 Chromosome 5, 110092411: 110092411
30 SLC25A46 NM_138773.3(SLC25A46): c.804G> A (p.Thr268=) single nucleotide variant Uncertain significance rs757342761 GRCh38 Chromosome 5, 110761329: 110761329
31 SLC25A46 NM_138773.3(SLC25A46): c.804G> A (p.Thr268=) single nucleotide variant Uncertain significance rs757342761 GRCh37 Chromosome 5, 110097029: 110097029
32 SLC25A46 NM_138773.3(SLC25A46): c.416C> A (p.Thr139Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs202123515 GRCh38 Chromosome 5, 110746300: 110746300
33 SLC25A46 NM_138773.3(SLC25A46): c.416C> A (p.Thr139Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs202123515 GRCh37 Chromosome 5, 110082001: 110082001
34 SLC25A46 NM_138773.3(SLC25A46): c.631G> A (p.Val211Met) single nucleotide variant Likely benign rs114859074 GRCh38 Chromosome 5, 110756712: 110756712
35 SLC25A46 NM_138773.3(SLC25A46): c.631G> A (p.Val211Met) single nucleotide variant Likely benign rs114859074 GRCh37 Chromosome 5, 110092412: 110092412
36 SLC25A46 NM_138773.3(SLC25A46): c.378A> G (p.Gln126=) single nucleotide variant Benign rs151055603 GRCh38 Chromosome 5, 110743781: 110743781
37 SLC25A46 NM_138773.3(SLC25A46): c.378A> G (p.Gln126=) single nucleotide variant Benign rs151055603 GRCh37 Chromosome 5, 110079482: 110079482
38 SLC25A46 NM_138773.3(SLC25A46): c.563+6A> T single nucleotide variant Benign rs114546039 GRCh38 Chromosome 5, 110748269: 110748269
39 SLC25A46 NM_138773.3(SLC25A46): c.563+6A> T single nucleotide variant Benign rs114546039 GRCh37 Chromosome 5, 110083970: 110083970
40 SLC25A46 NM_138773.3(SLC25A46): c.134C> T (p.Thr45Ile) single nucleotide variant Uncertain significance rs1554091122 GRCh38 Chromosome 5, 110739253: 110739253
41 SLC25A46 NM_138773.3(SLC25A46): c.134C> T (p.Thr45Ile) single nucleotide variant Uncertain significance rs1554091122 GRCh37 Chromosome 5, 110074954: 110074954
42 SLC25A46 NM_138773.3(SLC25A46): c.147C> T (p.Ile49=) single nucleotide variant Benign rs145421520 GRCh38 Chromosome 5, 110739266: 110739266
43 SLC25A46 NM_138773.3(SLC25A46): c.147C> T (p.Ile49=) single nucleotide variant Benign rs145421520 GRCh37 Chromosome 5, 110074967: 110074967
44 SLC25A46 NM_138773.3(SLC25A46): c.767A> G (p.Lys256Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs141213807 GRCh38 Chromosome 5, 110761292: 110761292
45 SLC25A46 NM_138773.3(SLC25A46): c.767A> G (p.Lys256Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs141213807 GRCh37 Chromosome 5, 110096992: 110096992
46 SLC25A46 NM_138773.3(SLC25A46): c.776T> G (p.Leu259Arg) single nucleotide variant Uncertain significance rs150754737 GRCh38 Chromosome 5, 110761301: 110761301
47 SLC25A46 NM_138773.3(SLC25A46): c.776T> G (p.Leu259Arg) single nucleotide variant Uncertain significance rs150754737 GRCh37 Chromosome 5, 110097001: 110097001
48 SLC25A46 NM_138773.3(SLC25A46): c.1137G> T (p.Glu379Asp) single nucleotide variant Benign rs79149180 GRCh38 Chromosome 5, 110761662: 110761662
49 SLC25A46 NM_138773.3(SLC25A46): c.1137G> T (p.Glu379Asp) single nucleotide variant Benign rs79149180 GRCh37 Chromosome 5, 110097362: 110097362
50 SLC25A46 NM_138773.3(SLC25A46): c.1248T> C (p.Asn416=) single nucleotide variant Likely benign rs776771749 GRCh38 Chromosome 5, 110761773: 110761773

Expression for Neuropathy, Hereditary Motor and Sensory, Type Vib

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Pathways for Neuropathy, Hereditary Motor and Sensory, Type Vib

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

Sources for Neuropathy, Hereditary Motor and Sensory, Type Vib

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