HMSN6B
MCID: NRP067
MIFTS: 28

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 56 29 6
Neuropathy, Hereditary Motor and Sensory, Type Vib 56 73 17
Hmsn Vib 56 73
Hmsn6b 56 73
Cmt6b 56 73
Neuropathy, Motor and Sensory, Hereditary, Type Vib 39
Hereditary Motor and Sensory Neuropathy Type Vib 73
Neuropathy, Hereditary Motor and Sensory, 6b 73
Charcot-Marie-Tooth Disease, Type 6b; Cmt6b 56
Charcot-Marie-Tooth Disease, Type 6b 56
Charcot-Marie-Tooth Disease 6b 73

Characteristics:

OMIM:

56
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:

31
neuropathy, hereditary motor and sensory, type vib, with optic atrophy:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



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

UniProtKB/Swiss-Prot : 73 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 : 56 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:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 occasional (7.5%) HP:0001251
2 hyperreflexia 31 occasional (7.5%) HP:0001347
3 babinski sign 31 occasional (7.5%) HP:0003487
4 cerebellar atrophy 31 occasional (7.5%) HP:0001272
5 respiratory failure 31 very rare (1%) HP:0002878
6 nystagmus 31 HP:0000639
7 muscle weakness 31 HP:0001324
8 tremor 31 HP:0001337
9 scoliosis 31 HP:0002650
10 narrow palate 31 HP:0000189
11 global developmental delay 31 HP:0001263
12 anteverted nares 31 HP:0000463
13 optic atrophy 31 HP:0000648
14 flexion contracture 31 HP:0001371
15 myoclonus 31 HP:0001336
16 narrow forehead 31 HP:0000341
17 generalized hypotonia 31 HP:0001290
18 tented upper lip vermilion 31 HP:0010804
19 progressive visual loss 31 HP:0000529
20 inverted nipples 31 HP:0003186
21 dysmetria 31 HP:0001310
22 pes cavus 31 HP:0001761
23 bulbous nose 31 HP:0000414
24 hyporeflexia 31 HP:0001265
25 tapered finger 31 HP:0001182
26 steppage gait 31 HP:0003376
27 distal sensory impairment 31 HP:0002936
28 exotropia 31 HP:0000577

Symptoms via clinical synopsis from OMIM:

56
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:

40
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. 56 6
27543974 2016
2
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. 56 6
27390132 2016
3
SLC25A46 mutations underlie progressive myoclonic ataxia with optic atrophy and neuropathy. 6 56
27430653 2016
4
Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. 6 56
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 Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC25A46 NM_138773.4(SLC25A46):c.166dup (p.His56fs)duplication Pathogenic 372237 rs1057519416 5:110074986-110074986 5:110739285-110739285
2 SLC25A46 NM_138773.4(SLC25A46):c.746G>A (p.Gly249Asp)SNV Pathogenic 372238 rs200725073 5:110096971-110096971 5:110761271-110761271
3 SLC25A46 NM_138773.4(SLC25A46):c.1005A>T (p.Glu335Asp)SNV Pathogenic 372239 rs1057518748 5:110097230-110097230 5:110761530-110761530
4 SLC25A46 NM_138773.4(SLC25A46):c.882_885dup (p.Asn296fs)duplication Pathogenic 372240 rs1057518749 5:110097107-110097110 5:110761407-110761410
5 SLC25A46 NM_138773.4(SLC25A46):c.998C>T (p.Pro333Leu)SNV Pathogenic 372241 rs1057518750 5:110097223-110097223 5:110761523-110761523
6 SLC25A46 NM_138773.4(SLC25A46):c.1018C>T (p.Arg340Cys)SNV Pathogenic 372242 rs746681765 5:110097243-110097243 5:110761543-110761543
7 SLC25A46 SCL25A46, 1.897-KB DELdeletion Pathogenic 374891
8 SLC25A46 NM_138773.4(SLC25A46):c.1022T>C (p.Leu341Pro)SNV Pathogenic 374892 rs1057519294 5:110097247-110097247 5:110761547-110761547
9 SLC25A46 NM_138773.4(SLC25A46):c.413T>G (p.Leu138Arg)SNV Pathogenic 374893 rs1057519295 5:110081998-110081998 5:110746297-110746297
10 SLC25A46 NM_138773.4(SLC25A46):c.425C>T (p.Thr142Ile)SNV Pathogenic 374894 rs1057519296 5:110082010-110082010 5:110746309-110746309
11 SLC25A46 NM_138773.4(SLC25A46):c.47del (p.Gly16fs)deletion Pathogenic 655776 5:110074867-110074867 5:110739166-110739166
12 SLC25A46 NC_000005.9:g.(?_110079421)_(110079498_?)deldeletion Pathogenic 652950 5:110079421-110079498 5:110743720-110743797
13 SLC25A46 NM_138773.4(SLC25A46):c.736A>T (p.Arg246Ter)SNV Likely pathogenic 488599 rs1554093168 5:110096961-110096961 5:110761261-110761261
14 SLC25A46 NM_138773.4(SLC25A46):c.770G>A (p.Arg257Gln)SNV Likely pathogenic 559386 rs1184021143 5:110096995-110096995 5:110761295-110761295
15 SLC25A46 NC_000005.9:g.(?_110077728)_(110083984_?)dupduplication Likely pathogenic 584411 5:110077728-110083984 5:110742027-110748283
16 SLC25A46 NM_138773.4(SLC25A46):c.803C>T (p.Thr268Met)SNV Conflicting interpretations of pathogenicity 422421 rs751900293 5:110097028-110097028 5:110761328-110761328
17 SLC25A46 NM_138773.4(SLC25A46):c.416C>A (p.Thr139Asn)SNV Conflicting interpretations of pathogenicity 475795 rs202123515 5:110082001-110082001 5:110746300-110746300
18 SLC25A46 NM_138773.4(SLC25A46):c.767A>G (p.Lys256Arg)SNV Conflicting interpretations of pathogenicity 475800 rs141213807 5:110096992-110096992 5:110761292-110761292
19 SLC25A46 NM_138773.4(SLC25A46):c.776T>G (p.Leu259Arg)SNV Uncertain significance 475801 rs150754737 5:110097001-110097001 5:110761301-110761301
20 SLC25A46 NM_138773.4(SLC25A46):c.134C>T (p.Thr45Ile)SNV Uncertain significance 475790 rs1554091122 5:110074954-110074954 5:110739253-110739253
21 SLC25A46 NM_138773.4(SLC25A46):c.196G>T (p.Val66Leu)SNV Uncertain significance 475792 rs758140632 5:110075016-110075016 5:110739315-110739315
22 SLC25A46 NM_138773.4(SLC25A46):c.50G>A (p.Gly17Asp)SNV Uncertain significance 565817 rs1561595689 5:110074870-110074870 5:110739169-110739169
23 SLC25A46 NM_138773.4(SLC25A46):c.55C>A (p.Arg19=)SNV Uncertain significance 580231 rs1186440654 5:110074875-110074875 5:110739174-110739174
24 SLC25A46 NM_138773.4(SLC25A46):c.458C>A (p.Thr153Asn)SNV Uncertain significance 582594 5:110082043-110082043 5:110746342-110746342
25 SLC25A46 NM_138773.4(SLC25A46):c.1135G>C (p.Glu379Gln)SNV Uncertain significance 568249 5:110097360-110097360 5:110761660-110761660
26 SLC25A46 NM_138773.4(SLC25A46):c.849G>C (p.Gln283His)SNV Uncertain significance 575114 5:110097074-110097074 5:110761374-110761374
27 SLC25A46 NM_138773.4(SLC25A46):c.23G>C (p.Gly8Ala)SNV Uncertain significance 571245 5:110074843-110074843 5:110739142-110739142
28 SLC25A46 NM_138773.4(SLC25A46):c.598G>A (p.Gly200Arg)SNV Uncertain significance 567704 5:110091199-110091199 5:110755499-110755499
29 SLC25A46 NM_138773.4(SLC25A46):c.1213A>G (p.Ile405Val)SNV Uncertain significance 583282 rs1561610274 5:110097438-110097438 5:110761738-110761738
30 SLC25A46 NM_138773.4(SLC25A46):c.63G>T (p.Glu21Asp)SNV Uncertain significance 577726 rs1561595734 5:110074883-110074883 5:110739182-110739182
31 SLC25A46 NM_138773.4(SLC25A46):c.385G>A (p.Val129Ile)SNV Uncertain significance 570174 5:110081970-110081970 5:110746269-110746269
32 SLC25A46 NM_138773.4(SLC25A46):c.410A>G (p.His137Arg)SNV Uncertain significance 570160 5:110081995-110081995 5:110746294-110746294
33 SLC25A46 NM_138773.4(SLC25A46):c.620C>A (p.Ser207Tyr)SNV Uncertain significance 582200 5:110091221-110091221 5:110755521-110755521
34 SLC25A46 NM_138773.4(SLC25A46):c.1036A>G (p.Thr346Ala)SNV Uncertain significance 574924 rs1561610023 5:110097261-110097261 5:110761561-110761561
35 SLC25A46 NM_138773.4(SLC25A46):c.1070A>G (p.Tyr357Cys)SNV Uncertain significance 577032 rs1229680117 5:110097295-110097295 5:110761595-110761595
36 SLC25A46 NM_138773.4(SLC25A46):c.804G>A (p.Thr268=)SNV Uncertain significance 475802 rs757342761 5:110097029-110097029 5:110761329-110761329
37 SLC25A46 NM_138773.4(SLC25A46):c.44G>A (p.Arg15Gln)SNV Uncertain significance 542449 rs372382932 5:110074864-110074864 5:110739163-110739163
38 SLC25A46 NM_138773.4(SLC25A46):c.46G>T (p.Gly16Cys)SNV Uncertain significance 542450 rs770562376 5:110074866-110074866 5:110739165-110739165
39 SLC25A46 NM_138773.4(SLC25A46):c.194G>C (p.Gly65Ala)SNV Uncertain significance 542452 rs1410055577 5:110075014-110075014 5:110739313-110739313
40 SLC25A46 NM_138773.4(SLC25A46):c.887A>G (p.Asn296Ser)SNV Uncertain significance 542448 rs201789237 5:110097112-110097112 5:110761412-110761412
41 SLC25A46 NM_138773.4(SLC25A46):c.100A>G (p.Ser34Gly)SNV Uncertain significance 664148 5:110074920-110074920 5:110739219-110739219
42 SLC25A46 NM_138773.4(SLC25A46):c.169T>C (p.Trp57Arg)SNV Uncertain significance 641076 5:110074989-110074989 5:110739288-110739288
43 SLC25A46 NM_138773.4(SLC25A46):c.247A>G (p.Ser83Gly)SNV Uncertain significance 661561 5:110075067-110075067 5:110739366-110739366
44 SLC25A46 NM_138773.4(SLC25A46):c.313A>G (p.Ile105Val)SNV Uncertain significance 648394 5:110077777-110077777 5:110742076-110742076
45 SLC25A46 NM_138773.4(SLC25A46):c.313A>T (p.Ile105Phe)SNV Uncertain significance 652335 5:110077777-110077777 5:110742076-110742076
46 SLC25A46 NM_138773.4(SLC25A46):c.322G>A (p.Ala108Thr)SNV Uncertain significance 663802 5:110077786-110077786 5:110742085-110742085
47 SLC25A46 NM_138773.4(SLC25A46):c.359G>T (p.Cys120Phe)SNV Uncertain significance 653726 5:110079463-110079463 5:110743762-110743762
48 SLC25A46 NM_138773.4(SLC25A46):c.579A>T (p.Lys193Asn)SNV Uncertain significance 661801 5:110091180-110091180 5:110755480-110755480
49 SLC25A46 NM_138773.4(SLC25A46):c.938_940del (p.Tyr313del)deletion Uncertain significance 644999 5:110097161-110097163 5:110761463-110761465
50 SLC25A46 NM_138773.4(SLC25A46):c.955G>C (p.Ala319Pro)SNV Uncertain significance 651121 5:110097180-110097180 5:110761480-110761480

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

73
# 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...

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

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