HMSN6B
MCID: NRP067
MIFTS: 27

Neuropathy, Hereditary Motor and Sensory, Type Vib, with Optic Atrophy (HMSN6B)

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

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

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

Name: Neuropathy, Hereditary Motor and Sensory, Type Vib, with Optic Atrophy 57 29 6
Neuropathy, Hereditary Motor and Sensory, Type Vib 57 74 17
Hmsn Vib 57 74
Hmsn6b 57 74
Cmt6b 57 74
Neuropathy, Motor and Sensory, Hereditary, Type Vib 40
Hereditary Motor and Sensory Neuropathy Type Vib 74
Neuropathy, Hereditary Motor and Sensory, 6b 74
Charcot-Marie-Tooth Disease, Type 6b; Cmt6b 57
Charcot-Marie-Tooth Disease, Type 6b 57
Charcot-Marie-Tooth Disease 6b 74

Characteristics:

OMIM:

57
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:

32
neuropathy, hereditary motor and sensory, type vib, with optic atrophy:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



External Ids:

OMIM 57 616505

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

UniProtKB/Swiss-Prot : 74 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, with Optic Atrophy, is also known as neuropathy, hereditary motor and sensory, type vib. An important gene associated with Neuropathy, Hereditary Motor and Sensory, Type Vib, with Optic Atrophy is SLC25A46 (Solute Carrier Family 25 Member 46). Affiliated tissues include brain and cerebellum, and related phenotypes are ataxia and hyperreflexia

OMIM : 57 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, 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

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

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

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 ataxia 32 occasional (7.5%) HP:0001251
2 hyperreflexia 32 occasional (7.5%) HP:0001347
3 babinski sign 32 occasional (7.5%) HP:0003487
4 cerebellar atrophy 32 occasional (7.5%) HP:0001272
5 respiratory failure 32 very rare (1%) HP:0002878
6 nystagmus 32 HP:0000639
7 muscle weakness 32 HP:0001324
8 tremor 32 HP:0001337
9 scoliosis 32 HP:0002650
10 narrow palate 32 HP:0000189
11 global developmental delay 32 HP:0001263
12 anteverted nares 32 HP:0000463
13 optic atrophy 32 HP:0000648
14 flexion contracture 32 HP:0001371
15 narrow forehead 32 HP:0000341
16 generalized hypotonia 32 HP:0001290
17 tented upper lip vermilion 32 HP:0010804
18 progressive visual loss 32 HP:0000529
19 myoclonus 32 HP:0001336
20 inverted nipples 32 HP:0003186
21 dysmetria 32 HP:0001310
22 pes cavus 32 HP:0001761
23 bulbous nose 32 HP:0000414
24 hyporeflexia 32 HP:0001265
25 tapered finger 32 HP:0001182
26 steppage gait 32 HP:0003376
27 distal sensory impairment 32 HP:0002936
28 exotropia 32 HP:0000577

Symptoms via clinical synopsis from OMIM:

57
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, with Optic...

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

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

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

# Genetic test Affiliating Genes
1 Neuropathy, Hereditary Motor and Sensory, Type Vib, with Optic Atrophy 29 SLC25A46

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

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

41
Brain, Cerebellum

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

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

# Title Authors PMID Year
1
Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. 8 71
27543974 2016
2
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. 8 71
27390132 2016
3
SLC25A46 mutations underlie progressive myoclonic ataxia with optic atrophy and neuropathy. 8 71
27430653 2016
4
Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. 8 71
26168012 2015

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

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

6 (show top 50) (show all 74)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SLC25A46 NM_138773.4(SLC25A46): c.166dup (p.His56fs) duplication Pathogenic rs1057519416 5:110074986-110074986 5:110739285-110739285
2 SLC25A46 NM_138773.4(SLC25A46): c.746G> A (p.Gly249Asp) single nucleotide variant Pathogenic rs200725073 5:110096971-110096971 5:110761271-110761271
3 SLC25A46 NM_138773.4(SLC25A46): c.1005A> T (p.Glu335Asp) single nucleotide variant Pathogenic rs1057518748 5:110097230-110097230 5:110761530-110761530
4 SLC25A46 NM_138773.4(SLC25A46): c.882_885dup (p.Asn296fs) duplication Pathogenic rs1057518749 5:110097107-110097110 5:110761407-110761410
5 SLC25A46 NM_138773.4(SLC25A46): c.998C> T (p.Pro333Leu) single nucleotide variant Pathogenic rs1057518750 5:110097223-110097223 5:110761523-110761523
6 SLC25A46 NM_138773.4(SLC25A46): c.1018C> T (p.Arg340Cys) single nucleotide variant Pathogenic rs746681765 5:110097243-110097243 5:110761543-110761543
7 SLC25A46 SCL25A46, 1.897-KB DEL deletion Pathogenic
8 SLC25A46 NM_138773.4(SLC25A46): c.1022T> C (p.Leu341Pro) single nucleotide variant Pathogenic rs1057519294 5:110097247-110097247 5:110761547-110761547
9 SLC25A46 NM_138773.4(SLC25A46): c.413T> G (p.Leu138Arg) single nucleotide variant Pathogenic rs1057519295 5:110081998-110081998 5:110746297-110746297
10 SLC25A46 NM_138773.4(SLC25A46): c.425C> T (p.Thr142Ile) single nucleotide variant Pathogenic rs1057519296 5:110082010-110082010 5:110746309-110746309
11 SLC25A46 NC_000005.9: g.(?_110079421)_(110079498_?)del deletion Pathogenic 5:110079421-110079498 5:110743720-110743797
12 SLC25A46 NM_138773.4(SLC25A46): c.47del (p.Gly16fs) deletion Pathogenic 5:110074867-110074867 5:110739166-110739166
13 SLC25A46 NM_138773.4(SLC25A46): c.736A> T (p.Arg246Ter) single nucleotide variant Likely pathogenic rs1554093168 5:110096961-110096961 5:110761261-110761261
14 SLC25A46 NM_138773.4(SLC25A46): c.770G> A (p.Arg257Gln) single nucleotide variant Likely pathogenic rs1184021143 5:110096995-110096995 5:110761295-110761295
15 SLC25A46 NC_000005.9: g.(?_110077728)_(110083984_?)dup duplication Likely pathogenic 5:110077728-110083984 5:110742027-110748283
16 SLC25A46 NM_138773.4(SLC25A46): c.767A> G (p.Lys256Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs141213807 5:110096992-110096992 5:110761292-110761292
17 SLC25A46 NM_138773.4(SLC25A46): c.803C> T (p.Thr268Met) single nucleotide variant Conflicting interpretations of pathogenicity rs751900293 5:110097028-110097028 5:110761328-110761328
18 SLC25A46 NM_138773.4(SLC25A46): c.416C> A (p.Thr139Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs202123515 5:110082001-110082001 5:110746300-110746300
19 SLC25A46 NM_138773.4(SLC25A46): c.776T> G (p.Leu259Arg) single nucleotide variant Uncertain significance rs150754737 5:110097001-110097001 5:110761301-110761301
20 SLC25A46 NM_138773.4(SLC25A46): c.134C> T (p.Thr45Ile) single nucleotide variant Uncertain significance rs1554091122 5:110074954-110074954 5:110739253-110739253
21 SLC25A46 NM_138773.4(SLC25A46): c.44G> A (p.Arg15Gln) single nucleotide variant Uncertain significance rs372382932 5:110074864-110074864 5:110739163-110739163
22 SLC25A46 NM_138773.4(SLC25A46): c.46G> T (p.Gly16Cys) single nucleotide variant Uncertain significance rs770562376 5:110074866-110074866 5:110739165-110739165
23 SLC25A46 NM_138773.4(SLC25A46): c.50G> A (p.Gly17Asp) single nucleotide variant Uncertain significance 5:110074870-110074870 5:110739169-110739169
24 SLC25A46 NM_138773.4(SLC25A46): c.55C> A (p.Arg19=) single nucleotide variant Uncertain significance 5:110074875-110074875 5:110739174-110739174
25 SLC25A46 NM_138773.4(SLC25A46): c.458C> A (p.Thr153Asn) single nucleotide variant Uncertain significance 5:110082043-110082043 5:110746342-110746342
26 SLC25A46 NM_138773.4(SLC25A46): c.1135G> C (p.Glu379Gln) single nucleotide variant Uncertain significance 5:110097360-110097360 5:110761660-110761660
27 SLC25A46 NM_138773.4(SLC25A46): c.849G> C (p.Gln283His) single nucleotide variant Uncertain significance 5:110097074-110097074 5:110761374-110761374
28 SLC25A46 NM_138773.4(SLC25A46): c.23G> C (p.Gly8Ala) single nucleotide variant Uncertain significance 5:110074843-110074843 5:110739142-110739142
29 SLC25A46 NM_138773.4(SLC25A46): c.598G> A (p.Gly200Arg) single nucleotide variant Uncertain significance 5:110091199-110091199 5:110755499-110755499
30 SLC25A46 NM_138773.4(SLC25A46): c.1213A> G (p.Ile405Val) single nucleotide variant Uncertain significance 5:110097438-110097438 5:110761738-110761738
31 SLC25A46 NM_138773.4(SLC25A46): c.63G> T (p.Glu21Asp) single nucleotide variant Uncertain significance 5:110074883-110074883 5:110739182-110739182
32 SLC25A46 NM_138773.4(SLC25A46): c.385G> A (p.Val129Ile) single nucleotide variant Uncertain significance 5:110081970-110081970 5:110746269-110746269
33 SLC25A46 NM_138773.4(SLC25A46): c.410A> G (p.His137Arg) single nucleotide variant Uncertain significance 5:110081995-110081995 5:110746294-110746294
34 SLC25A46 NM_138773.4(SLC25A46): c.620C> A (p.Ser207Tyr) single nucleotide variant Uncertain significance 5:110091221-110091221 5:110755521-110755521
35 SLC25A46 NM_138773.4(SLC25A46): c.1036A> G (p.Thr346Ala) single nucleotide variant Uncertain significance 5:110097261-110097261 5:110761561-110761561
36 SLC25A46 NM_138773.4(SLC25A46): c.1070A> G (p.Tyr357Cys) single nucleotide variant Uncertain significance 5:110097295-110097295 5:110761595-110761595
37 SLC25A46 NM_138773.4(SLC25A46): c.463-3del deletion Uncertain significance
38 SLC25A46 NM_138773.4(SLC25A46): c.804G> A (p.Thr268=) single nucleotide variant Uncertain significance rs757342761 5:110097029-110097029 5:110761329-110761329
39 SLC25A46 NM_138773.4(SLC25A46): c.620+4_620+7del deletion Uncertain significance
40 SLC25A46 NM_138773.4(SLC25A46): c.284-3T> C single nucleotide variant Uncertain significance 5:110077745-110077745 5:110742044-110742044
41 SLC25A46 NM_138773.4(SLC25A46): c.678+3G> A single nucleotide variant Uncertain significance 5:110092462-110092462 5:110756762-110756762
42 SLC25A46 NM_138773.4(SLC25A46): c.148C> A (p.Pro50Thr) single nucleotide variant Uncertain significance rs147648476 5:110074968-110074968 5:110739267-110739267
43 SLC25A46 NM_138773.4(SLC25A46): c.427G> A (p.Val143Ile) single nucleotide variant Uncertain significance rs1554092069 5:110082012-110082012 5:110746311-110746311
44 SLC25A46 NM_138773.4(SLC25A46): c.194G> C (p.Gly65Ala) single nucleotide variant Uncertain significance rs1410055577 5:110075014-110075014 5:110739313-110739313
45 SLC25A46 NM_138773.4(SLC25A46): c.887A> G (p.Asn296Ser) single nucleotide variant Uncertain significance rs201789237 5:110097112-110097112 5:110761412-110761412
46 SLC25A46 NM_138773.4(SLC25A46): c.371G> A (p.Arg124His) single nucleotide variant Uncertain significance rs756258729 5:110079475-110079475 5:110743774-110743774
47 SLC25A46 NM_138773.4(SLC25A46): c.196G> T (p.Val66Leu) single nucleotide variant Uncertain significance rs758140632 5:110075016-110075016 5:110739315-110739315
48 SLC25A46 NM_138773.4(SLC25A46): c.1072G> C (p.Glu358Gln) single nucleotide variant Uncertain significance 5:110097297-110097297 5:110761597-110761597
49 SLC25A46 NM_138773.4(SLC25A46): c.1063C> G (p.Leu355Val) single nucleotide variant Uncertain significance 5:110097288-110097288 5:110761588-110761588
50 SLC25A46 NM_138773.4(SLC25A46): c.977G> T (p.Cys326Phe) single nucleotide variant Uncertain significance 5:110097202-110097202 5:110761502-110761502

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

74
# 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

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

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

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

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

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