SPG74
MCID: SPS156
MIFTS: 26

Spastic Paraplegia 74, Autosomal Recessive (SPG74)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 74, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 74, Autosomal Recessive:

Name: Spastic Paraplegia 74, Autosomal Recessive 57 72 29 6
Spg74 57 12 58 72
Paraplegia, Spastic, Autosomal Recessive, Type 74 39
Autosomal Recessive Spastic Paraplegia Type 74 58
Autosomal Recessive Spastic Paraplegia 74 12
Hereditary Spastic Paraplegia 74 12

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
onset in first decade
one consanguineous arab family has been reported (last curated july 2015)


HPO:

31
spastic paraplegia 74, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Spastic Paraplegia 74, Autosomal Recessive

UniProtKB/Swiss-Prot : 72 Spastic paraplegia 74, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG74 is characterized by a combination of spastic paraplegia, optic atrophy, and peripheral neuropathy with childhood-onset and slow progression into late adulthood.

MalaCards based summary : Spastic Paraplegia 74, Autosomal Recessive, is also known as spg74. An important gene associated with Spastic Paraplegia 74, Autosomal Recessive is IBA57 (Iron-Sulfur Cluster Assembly Factor IBA57). Affiliated tissues include eye, and related phenotypes are peripheral axonal neuropathy and progressive spastic paraplegia

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the IBA57 gene on chromosome 1q42.

OMIM® : 57 Spastic paraplegia-74 is an autosomal recessive neurologic disorder characterized by onset of slowly progressive lower limb spasticity, optic atrophy, and peripheral neuropathy in the first decade (summary by Lossos et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). (616451) (Updated 05-Apr-2021)

Related Diseases for Spastic Paraplegia 74, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Dominant
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 10
Spastic Paraplegia 12 Spastic Paraplegia 13
Spastic Paraplegia 14 Spastic Paraplegia 15
Spastic Paraplegia 16 Spastic Paraplegia 17
Spastic Paraplegia 18 Spastic Paraplegia 19
Spastic Paraplegia 24 Spastic Paraplegia 25
Spastic Paraplegia 26 Spastic Paraplegia 29
Spastic Paraplegia 3 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Spastic Paraplegia Type 49 Autosomal Recessive Spastic Paraplegia Type 60
Autosomal Recessive Spastic Paraplegia Type 59 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67
Autosomal Dominant Spastic Paraplegia Type 9b

Symptoms & Phenotypes for Spastic Paraplegia 74, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 74, Autosomal Recessive:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 peripheral axonal neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003477
2 progressive spastic paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007020
3 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
4 distal lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009053
5 decreased activity of mitochondrial complex i 58 31 frequent (33%) Frequent (79-30%) HP:0011923
6 visual field defect 58 31 frequent (33%) Frequent (79-30%) HP:0001123
7 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
8 distal amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003693
9 emg: neuropathic changes 58 31 frequent (33%) Frequent (79-30%) HP:0003445
10 distal peripheral sensory neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007067
11 decreased achilles reflex 58 31 frequent (33%) Frequent (79-30%) HP:0009072
12 hyperactive patellar reflex 58 31 frequent (33%) Frequent (79-30%) HP:0007083
13 decreased activity of mitochondrial complex ii 58 31 frequent (33%) Frequent (79-30%) HP:0008314
14 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
15 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
16 hypoplasia of the corpus callosum 58 31 very rare (1%) Very rare (<4-1%) HP:0002079
17 cerebellar atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0001272
18 cerebral white matter atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0012762
19 hyperreflexia 31 HP:0001347
20 visual impairment 58 Frequent (79-30%)
21 areflexia 31 HP:0001284
22 spastic paraplegia 31 HP:0001258
23 distal sensory impairment 31 HP:0002936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
visual impairment
optic atrophy
visual field defects

Neurologic Peripheral Nervous System:
distal sensory impairment
axonal peripheral neuropathy
areflexia of the ankles
reduced compound muscle action potentials and velocities

Laboratory Abnormalities:
patient lymphoblastoid cells showed decreased activity of mitochondrial complexes i and ii

Neurologic Central Nervous System:
spastic paraplegia
extensor plantar responses
hyperreflexia of the knee

Muscle Soft Tissue:
distal leg muscle atrophy

Clinical features from OMIM®:

616451 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spastic Paraplegia 74, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 74, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 74, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 74, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 74, Autosomal Recessive 29 IBA57

Anatomical Context for Spastic Paraplegia 74, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 74, Autosomal Recessive:

40
Eye

Publications for Spastic Paraplegia 74, Autosomal Recessive

Articles related to Spastic Paraplegia 74, Autosomal Recessive:

# Title Authors PMID Year
1
Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. 6 57
25609768 2015
2
Phenotypic spectrum of mutations in IBA57, a candidate gene for cavitating leukoencephalopathy. 6
28671726 2018
3
Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes. 6
27785568 2017

Variations for Spastic Paraplegia 74, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 74, Autosomal Recessive:

6 (show all 34)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 IBA57 NM_001010867.4(IBA57):c.678A>G (p.Gln226=) SNV Pathogenic 203449 rs876657407 GRCh37: 1:228362729-228362729
GRCh38: 1:228175028-228175028
2 IBA57 NM_001010867.4(IBA57):c.384dup (p.Asp129Ter) Duplication Pathogenic 660906 rs1571918251 GRCh37: 1:228362434-228362435
GRCh38: 1:228174733-228174734
3 IBA57 NM_001010867.4(IBA57):c.341+1G>A SNV Likely pathogenic 948465 GRCh37: 1:228353859-228353859
GRCh38: 1:228166158-228166158
4 IBA57 NM_001010867.4(IBA57):c.85T>G (p.Cys29Gly) SNV Uncertain significance 662694 rs951070079 GRCh37: 1:228353602-228353602
GRCh38: 1:228165901-228165901
5 IBA57 NM_001010867.4(IBA57):c.335T>G (p.Leu112Trp) SNV Uncertain significance 541311 rs775646159 GRCh37: 1:228353852-228353852
GRCh38: 1:228166151-228166151
6 IBA57 NM_001010867.4(IBA57):c.206T>C (p.Phe69Ser) SNV Uncertain significance 541312 rs778284446 GRCh37: 1:228353723-228353723
GRCh38: 1:228166022-228166022
7 IBA57 NM_001010867.4(IBA57):c.1033G>A (p.Ala345Thr) SNV Uncertain significance 572919 rs150912462 GRCh37: 1:228363176-228363176
GRCh38: 1:228175475-228175475
8 IBA57 NM_001010867.4(IBA57):c.215G>C (p.Gly72Ala) SNV Uncertain significance 574590 rs1420144150 GRCh37: 1:228353732-228353732
GRCh38: 1:228166031-228166031
9 IBA57 NM_001010867.4(IBA57):c.354C>A (p.His118Gln) SNV Uncertain significance 579645 rs1315886237 GRCh37: 1:228362405-228362405
GRCh38: 1:228174704-228174704
10 IBA57 NM_001010867.4(IBA57):c.259G>A (p.Gly87Arg) SNV Uncertain significance 639514 rs1026408197 GRCh37: 1:228353776-228353776
GRCh38: 1:228166075-228166075
11 IBA57 NM_001010867.4(IBA57):c.262G>A (p.Ala88Thr) SNV Uncertain significance 655156 rs1186238890 GRCh37: 1:228353779-228353779
GRCh38: 1:228166078-228166078
12 IBA57 NM_001010867.4(IBA57):c.989C>G (p.Pro330Arg) SNV Uncertain significance 841605 GRCh37: 1:228363132-228363132
GRCh38: 1:228175431-228175431
13 IBA57 NM_001010867.4(IBA57):c.190C>A (p.Pro64Thr) SNV Uncertain significance 844143 GRCh37: 1:228353707-228353707
GRCh38: 1:228166006-228166006
14 IBA57 NM_001010867.4(IBA57):c.748A>G (p.Met250Val) SNV Uncertain significance 1005540 GRCh37: 1:228362891-228362891
GRCh38: 1:228175190-228175190
15 IBA57 NM_001010867.4(IBA57):c.341+4A>G SNV Uncertain significance 1008432 GRCh37: 1:228353862-228353862
GRCh38: 1:228166161-228166161
16 IBA57 NM_001010867.4(IBA57):c.316A>G (p.Thr106Ala) SNV Uncertain significance 545650 rs1053773776 GRCh37: 1:228353833-228353833
GRCh38: 1:228166132-228166132
17 IBA57 NM_001010867.4(IBA57):c.893C>T (p.Thr298Met) SNV Uncertain significance 937315 GRCh37: 1:228363036-228363036
GRCh38: 1:228175335-228175335
18 IBA57 NM_001010867.4(IBA57):c.434T>C (p.Ile145Thr) SNV Uncertain significance 1022231 GRCh37: 1:228362485-228362485
GRCh38: 1:228174784-228174784
19 IBA57 NM_001010867.4(IBA57):c.11C>T (p.Ala4Val) SNV Uncertain significance 651713 rs199781237 GRCh37: 1:228353528-228353528
GRCh38: 1:228165827-228165827
20 IBA57 NM_001010867.4(IBA57):c.599C>T (p.Thr200Ile) SNV Uncertain significance 559322 rs149136930 GRCh37: 1:228362650-228362650
GRCh38: 1:228174949-228174949
21 IBA57 NM_001010867.4(IBA57):c.599C>G (p.Thr200Ser) SNV Uncertain significance 863483 GRCh37: 1:228362650-228362650
GRCh38: 1:228174949-228174949
22 IBA57 NM_001010867.4(IBA57):c.232C>G (p.Leu78Val) SNV Uncertain significance 1028441 GRCh37: 1:228353749-228353749
GRCh38: 1:228166048-228166048
23 IBA57 NM_001010867.4(IBA57):c.574G>A (p.Ala192Thr) SNV Uncertain significance 1037759 GRCh37: 1:228362625-228362625
GRCh38: 1:228174924-228174924
24 IBA57 NM_001010867.4(IBA57):c.780C>T (p.Tyr260=) SNV Likely benign 508383 rs202126055 GRCh37: 1:228362923-228362923
GRCh38: 1:228175222-228175222
25 IBA57 NM_001010867.4(IBA57):c.961C>T (p.Leu321=) SNV Likely benign 541314 rs376206530 GRCh37: 1:228363104-228363104
GRCh38: 1:228175403-228175403
26 IBA57 NM_001010867.4(IBA57):c.680-5T>A SNV Likely benign 704824 rs577050962 GRCh37: 1:228362818-228362818
GRCh38: 1:228175117-228175117
27 IBA57 NM_001010867.4(IBA57):c.930C>G (p.Phe310Leu) SNV Likely benign 707076 rs142734560 GRCh37: 1:228363073-228363073
GRCh38: 1:228175372-228175372
28 IBA57 NM_001010867.4(IBA57):c.150C>T (p.Cys50=) SNV Likely benign 707654 rs765132163 GRCh37: 1:228353667-228353667
GRCh38: 1:228165966-228165966
29 IBA57 NM_001010867.4(IBA57):c.264C>G (p.Ala88=) SNV Likely benign 382792 rs13375853 GRCh37: 1:228353781-228353781
GRCh38: 1:228166080-228166080
30 IBA57 NM_001010867.4(IBA57):c.801C>T (p.Ala267=) SNV Likely benign 474297 rs138699407 GRCh37: 1:228362944-228362944
GRCh38: 1:228175243-228175243
31 IBA57 NM_001010867.4(IBA57):c.462C>T (p.His154=) SNV Benign 381420 rs148398789 GRCh37: 1:228362513-228362513
GRCh38: 1:228174812-228174812
32 IBA57 NM_001010867.4(IBA57):c.210G>C (p.Leu70=) SNV Benign 559321 rs199589485 GRCh37: 1:228353727-228353727
GRCh38: 1:228166026-228166026
33 IBA57 NM_001010867.4(IBA57):c.980T>C (p.Ile327Thr) SNV Benign 559323 rs61745091 GRCh37: 1:228363123-228363123
GRCh38: 1:228175422-228175422
34 IBA57 NM_001010867.4(IBA57):c.645C>T (p.Asp215=) SNV Benign 541313 rs61743941 GRCh37: 1:228362696-228362696
GRCh38: 1:228174995-228174995

Expression for Spastic Paraplegia 74, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 74, Autosomal Recessive.

Pathways for Spastic Paraplegia 74, Autosomal Recessive

GO Terms for Spastic Paraplegia 74, Autosomal Recessive

Sources for Spastic Paraplegia 74, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
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44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
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53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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