MCID: SPS103
MIFTS: 38

Spastic Paraplegia 50, Autosomal Recessive

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Metabolic diseases

Aliases & Classifications for Spastic Paraplegia 50, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 50, Autosomal Recessive:

Name: Spastic Paraplegia 50, Autosomal Recessive 57 75 29 13 6
Spg50 57 12 75
Hereditary Spastic Paraplegia 50 12 15
Cerebral Palsy, Spastic Quadriplegic, 3, Formerly; Cpsq3, Formerly 57
Paraplegia, Spastic, Autosomal Recessive, Type 50 ) 40
Cerebral Palsy, Spastic Quadriplegic, 3, Formerly 57
Spastic Paraplegia-50, Autosomal Recessive 73
Autosomal Recessive Spastic Paraplegia 50 12
Spastic Quadriplegic Cerebral Palsy 3 12
Cpsq3, Formerly 57
Cpsq3 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth or prenatally


HPO:

32
spastic paraplegia 50, autosomal recessive:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spastic Paraplegia 50, Autosomal Recessive

UniProtKB/Swiss-Prot : 75 Spastic paraplegia 50, 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. SPG50 affected individuals present postnatally with early infantile hypotonia, delayed psychomotor development, strabismus, lack of independent walking and severe mental retardation. They develop progressive spasticity of all limbs with generalized hypertonia, hyperreflexia, and extensor plantar responses by the end of the first year of life. Speech is absent or limited. Pseudobulbar signs, such as drooling, stereotypic laughter, and exaggerated jaw jerk, are part of the clinical picture.

MalaCards based summary : Spastic Paraplegia 50, Autosomal Recessive, also known as spg50, is related to cerebral palsy, spastic quadriplegic, 3 and spastic paraplegia 56, autosomal recessive, and has symptoms including seizures and pseudobulbar signs. An important gene associated with Spastic Paraplegia 50, Autosomal Recessive is AP4M1 (Adaptor Related Protein Complex 4 Subunit Mu 1), and among its related pathways/superpathways are Clathrin derived vesicle budding and Lysosome. Related phenotypes are wide mouth and high palate

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the AP4M1 gene on chromosome 7q22.1.

OMIM : 57 Spastic paraplegia-50 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development (summary by Verkerk et al., 2009). (612936)

Related Diseases for Spastic Paraplegia 50, 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 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 Recessive
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 Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia 51 Hereditary Spastic Paraplegia 72
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 1
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 31 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 51
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 68 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

Diseases related to Spastic Paraplegia 50, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 cerebral palsy, spastic quadriplegic, 3 11.6
2 spastic paraplegia 56, autosomal recessive 9.8 AP4S1 RTN2
3 spastic paraplegia 47, autosomal recessive 9.6 AP4B1 AP5Z1
4 severe intellectual disability and progressive spastic paraplegia 9.5 AP4B1 AP4M1 AP4S1
5 cerebral palsy 9.5 AP4B1 AP4M1 AP4S1
6 spastic paraplegia 33, autosomal dominant 9.5 AP5Z1 RTN2
7 spastic paraplegia 31, autosomal dominant 9.4 AP5Z1 RTN2
8 spastic paraplegia 2, x-linked 9.4 AP5Z1 RTN2
9 spastic paraplegia 12, autosomal dominant 9.3 AP5Z1 RTN2
10 spastic paraplegia 10, autosomal dominant 9.2 AP5Z1 RTN2
11 trehalase deficiency 9.1 AP4B1 AP4M1 AP4S1
12 spastic paraplegia 54, autosomal recessive 8.9 AP4S1 AP5Z1 RTN2
13 paraplegia 8.9 AP5Z1 RTN2
14 hereditary spastic paraplegia 8.4 AP4B1 AP4M1 AP5Z1 RTN2
15 hereditary spastic paraplegia 51 8.4 AP4B1 AP4S1 AP5Z1 RTN2
16 spastic paraplegia 52, autosomal recessive 8.3 AP4B1 AP4S1 AP5Z1 RTN2
17 spastic paraplegia 28, autosomal recessive 8.3 AP4B1 AP4S1 AP5Z1 RTN2

Graphical network of the top 20 diseases related to Spastic Paraplegia 50, Autosomal Recessive:



Diseases related to Spastic Paraplegia 50, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 50, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
hyperreflexia
hypertonia
ventriculomegaly
cerebellar atrophy
more
Head And Neck Eyes:
strabismus

Head And Neck Face:
short philtrum
drooling
pseudobulbar signs
coarse face
bitemporal narrowing
more
Skeletal Hands:
adducted thumbs

Head And Neck Head:
microcephaly

Head And Neck Mouth:
wide mouth
high-arched palate
everted upper vermilion
prominent jaw reflex

Head And Neck Nose:
bulbous nose
broad nasal ridge

Skeletal Feet:
club feet


Clinical features from OMIM:

612936

Human phenotypes related to Spastic Paraplegia 50, Autosomal Recessive:

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 wide mouth 32 HP:0000154
2 high palate 32 HP:0000218
3 microcephaly 32 HP:0000252
4 coarse facial features 32 HP:0000280
5 mandibular prognathia 32 HP:0000303
6 short philtrum 32 HP:0000322
7 narrow forehead 32 HP:0000341
8 bulbous nose 32 HP:0000414
9 strabismus 32 HP:0000486
10 adducted thumb 32 HP:0001181
11 seizures 32 HP:0001250
12 spastic paraplegia 32 HP:0001258
13 global developmental delay 32 HP:0001263
14 cerebellar atrophy 32 HP:0001272
15 neonatal hypotonia 32 HP:0001319
16 hyperreflexia 32 HP:0001347
17 talipes equinovarus 32 HP:0001762
18 hypoplasia of the corpus callosum 32 HP:0002079
19 ventriculomegaly 32 HP:0002119
20 gliosis 32 HP:0002171
21 pseudobulbar signs 32 HP:0002200
22 drooling 32 HP:0002307
23 spastic tetraplegia 32 HP:0002510
24 babinski sign 32 HP:0003487
25 intellectual disability, progressive 32 HP:0006887
26 intellectual disability, severe 32 HP:0010864
27 wide nasal ridge 32 HP:0012811
28 cerebral palsy 32 HP:0100021

UMLS symptoms related to Spastic Paraplegia 50, Autosomal Recessive:


seizures, pseudobulbar signs

Drugs & Therapeutics for Spastic Paraplegia 50, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 50, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 50, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 50, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 50, Autosomal Recessive 29 AP4M1

Anatomical Context for Spastic Paraplegia 50, Autosomal Recessive

Publications for Spastic Paraplegia 50, Autosomal Recessive

Variations for Spastic Paraplegia 50, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 50, Autosomal Recessive:

6
(show all 43)
# Gene Variation Type Significance SNP ID Assembly Location
1 AP4M1 AP4M1, IVS14DS, G-T, +1 single nucleotide variant Pathogenic
2 AP4M1 NM_004722.3(AP4M1): c.577G> A (p.Glu193Lys) single nucleotide variant Pathogenic rs387906838 GRCh37 Chromosome 7, 99701748: 99701748
3 AP4M1 NM_004722.3(AP4M1): c.577G> A (p.Glu193Lys) single nucleotide variant Pathogenic rs387906838 GRCh38 Chromosome 7, 100104125: 100104125
4 AP4M1 NM_004722.3(AP4M1): c.952C> T (p.Arg318Ter) single nucleotide variant Pathogenic/Likely pathogenic rs730882249 GRCh38 Chromosome 7, 100105981: 100105981
5 AP4M1 NM_004722.3(AP4M1): c.952C> T (p.Arg318Ter) single nucleotide variant Pathogenic/Likely pathogenic rs730882249 GRCh37 Chromosome 7, 99703604: 99703604
6 AP4M1 NM_004722.3(AP4M1): c.1012C> T (p.Arg338Ter) single nucleotide variant Pathogenic rs146262009 GRCh38 Chromosome 7, 100106278: 100106278
7 AP4M1 NM_004722.3(AP4M1): c.1012C> T (p.Arg338Ter) single nucleotide variant Pathogenic rs146262009 GRCh37 Chromosome 7, 99703901: 99703901
8 AP4M1 NM_004722.3(AP4M1): c.32delA (p.Lys11Argfs) deletion Likely pathogenic rs797045249 GRCh37 Chromosome 7, 99699369: 99699369
9 AP4M1 NM_004722.3(AP4M1): c.32delA (p.Lys11Argfs) deletion Likely pathogenic rs797045249 GRCh38 Chromosome 7, 100101746: 100101746
10 AP4M1 NM_004722.3(AP4M1): c.228C> T (p.Pro76=) single nucleotide variant Benign rs41280965 GRCh38 Chromosome 7, 100102755: 100102755
11 AP4M1 NM_004722.3(AP4M1): c.228C> T (p.Pro76=) single nucleotide variant Benign rs41280965 GRCh37 Chromosome 7, 99700378: 99700378
12 AP4M1 NM_004722.3(AP4M1): c.333A> C (p.Glu111Asp) single nucleotide variant Uncertain significance rs138437966 GRCh37 Chromosome 7, 99700565: 99700565
13 AP4M1 NM_004722.3(AP4M1): c.333A> C (p.Glu111Asp) single nucleotide variant Uncertain significance rs138437966 GRCh38 Chromosome 7, 100102942: 100102942
14 AP4M1 NM_004722.3(AP4M1): c.930G> A (p.Arg310=) single nucleotide variant Conflicting interpretations of pathogenicity rs141754568 GRCh37 Chromosome 7, 99703582: 99703582
15 AP4M1 NM_004722.3(AP4M1): c.930G> A (p.Arg310=) single nucleotide variant Conflicting interpretations of pathogenicity rs141754568 GRCh38 Chromosome 7, 100105959: 100105959
16 AP4M1 NM_004722.3(AP4M1): c.740G> C (p.Gly247Ala) single nucleotide variant Benign/Likely benign rs145887263 GRCh38 Chromosome 7, 100105252: 100105252
17 AP4M1 NM_004722.3(AP4M1): c.740G> C (p.Gly247Ala) single nucleotide variant Benign/Likely benign rs145887263 GRCh37 Chromosome 7, 99702875: 99702875
18 AP4M1 NM_004722.3(AP4M1): c.163C> T (p.His55Tyr) single nucleotide variant Uncertain significance rs578114705 GRCh37 Chromosome 7, 99700313: 99700313
19 AP4M1 NM_004722.3(AP4M1): c.163C> T (p.His55Tyr) single nucleotide variant Uncertain significance rs578114705 GRCh38 Chromosome 7, 100102690: 100102690
20 AP4M1 NM_004722.3(AP4M1): c.544-6T> G single nucleotide variant Conflicting interpretations of pathogenicity rs372511561 GRCh38 Chromosome 7, 100104086: 100104086
21 AP4M1 NM_004722.3(AP4M1): c.544-6T> G single nucleotide variant Conflicting interpretations of pathogenicity rs372511561 GRCh37 Chromosome 7, 99701709: 99701709
22 AP4M1 NM_004722.3(AP4M1): c.58+2T> G single nucleotide variant Likely pathogenic GRCh38 Chromosome 7, 100101774: 100101774
23 AP4M1 NM_004722.3(AP4M1): c.58+2T> G single nucleotide variant Likely pathogenic GRCh37 Chromosome 7, 99699397: 99699397
24 AP4M1 NM_004722.3(AP4M1): c.129C> A (p.Asp43Glu) single nucleotide variant Uncertain significance rs760835879 GRCh37 Chromosome 7, 99699573: 99699573
25 AP4M1 NM_004722.3(AP4M1): c.129C> A (p.Asp43Glu) single nucleotide variant Uncertain significance rs760835879 GRCh38 Chromosome 7, 100101950: 100101950
26 AP4M1 NM_004722.3(AP4M1): c.364G> A (p.Val122Ile) single nucleotide variant Uncertain significance rs572732241 GRCh38 Chromosome 7, 100103421: 100103421
27 AP4M1 NM_004722.3(AP4M1): c.364G> A (p.Val122Ile) single nucleotide variant Uncertain significance rs572732241 GRCh37 Chromosome 7, 99701044: 99701044
28 AP4M1 NM_004722.3(AP4M1): c.851A> C (p.Tyr284Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 7, 100105461: 100105461
29 AP4M1 NM_004722.3(AP4M1): c.851A> C (p.Tyr284Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 7, 99703084: 99703084
30 AP4M1 NM_004722.3(AP4M1): c.1195C> T (p.Pro399Ser) single nucleotide variant Uncertain significance rs773269627 GRCh38 Chromosome 7, 100106715: 100106715
31 AP4M1 NM_004722.3(AP4M1): c.1195C> T (p.Pro399Ser) single nucleotide variant Uncertain significance rs773269627 GRCh37 Chromosome 7, 99704338: 99704338
32 AP4M1 NM_004722.3(AP4M1): c.453C> T (p.Ser151=) single nucleotide variant Likely benign GRCh37 Chromosome 7, 99701133: 99701133
33 AP4M1 NM_004722.3(AP4M1): c.453C> T (p.Ser151=) single nucleotide variant Likely benign GRCh38 Chromosome 7, 100103510: 100103510
34 AP4M1 NM_004722.3(AP4M1): c.737delC (p.Pro246Glnfs) deletion Pathogenic GRCh37 Chromosome 7, 99702872: 99702872
35 AP4M1 NM_004722.3(AP4M1): c.737delC (p.Pro246Glnfs) deletion Pathogenic GRCh38 Chromosome 7, 100105249: 100105249
36 AP4M1 NM_004722.3(AP4M1): c.1225T> C (p.Phe409Leu) single nucleotide variant Pathogenic rs760907496 GRCh38 Chromosome 7, 100106745: 100106745
37 AP4M1 NM_004722.3(AP4M1): c.1225T> C (p.Phe409Leu) single nucleotide variant Pathogenic rs760907496 GRCh37 Chromosome 7, 99704368: 99704368
38 AP4M1 NM_004722.3(AP4M1): c.802C> T (p.Arg268Ter) single nucleotide variant Pathogenic rs780030221 GRCh38 Chromosome 7, 100105314: 100105314
39 AP4M1 NM_004722.3(AP4M1): c.802C> T (p.Arg268Ter) single nucleotide variant Pathogenic rs780030221 GRCh37 Chromosome 7, 99702937: 99702937
40 AP4M1 NM_004722.3(AP4M1): c.847C> T (p.Arg283Trp) single nucleotide variant Uncertain significance rs575096086 GRCh38 Chromosome 7, 100105457: 100105457
41 AP4M1 NM_004722.3(AP4M1): c.847C> T (p.Arg283Trp) single nucleotide variant Uncertain significance rs575096086 GRCh37 Chromosome 7, 99703080: 99703080
42 AP4M1 NM_004722.3(AP4M1): c.1002C> G (p.Leu334=) single nucleotide variant Likely benign rs140843407 GRCh38 Chromosome 7, 100106268: 100106268
43 AP4M1 NM_004722.3(AP4M1): c.1002C> G (p.Leu334=) single nucleotide variant Likely benign rs140843407 GRCh37 Chromosome 7, 99703891: 99703891

Expression for Spastic Paraplegia 50, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 50, Autosomal Recessive.

Pathways for Spastic Paraplegia 50, Autosomal Recessive

Pathways related to Spastic Paraplegia 50, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.51 AP4B1 AP4M1 AP4S1
2 10.89 AP4B1 AP4M1 AP4S1

GO Terms for Spastic Paraplegia 50, Autosomal Recessive

Cellular components related to Spastic Paraplegia 50, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 trans-Golgi network membrane GO:0032588 9.33 AP4B1 AP4M1 AP4S1
2 trans-Golgi network GO:0005802 9.32 AP4B1 AP4M1
3 clathrin adaptor complex GO:0030131 9.26 AP4B1 AP4M1
4 endosome lumen GO:0031904 9.13 AP4B1 AP4M1 AP4S1
5 AP-4 adaptor complex GO:0030124 8.8 AP4B1 AP4M1 AP4S1

Biological processes related to Spastic Paraplegia 50, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.46 AP4B1 AP4M1 AP4S1 AP5Z1
2 protein localization GO:0008104 9.13 AP4B1 AP4M1 AP4S1
3 protein targeting GO:0006605 8.8 AP4B1 AP4M1 AP4S1

Sources for Spastic Paraplegia 50, Autosomal Recessive

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11 DGIdb
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