SMALED1
MCID: SPN385
MIFTS: 28

Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant (SMALED1)

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

Aliases & Classifications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

MalaCards integrated aliases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

Name: Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant 58 54
Smaled1 58 54 60 76
Dync1h1-Related Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy 54 60
Dync1h1-Related Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy 54 60
Spinal Muscular Atrophy, Lower Extremity Predominant 1, Autosomal Dominant 30 6
Spinal Muscular Atrophy, Childhood, Proximal, Autosomal Dominant 58 74
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Ad 58 54
Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy Without Contractures 54
Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy Without Contractures 54
Autosomal Dominant Spinal Muscular Atrophy with Lower Extremity Predominance 54
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Autosomal Dominant 76
Autosomal Dominant Spinal Muscular Atrophy, Lower Extremity-Predominant 1 54
Autosomal Dominant Lower Extremity-Predominant Spinal Muscular Atrophy-1 54
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Dominant 54
Spinal Muscular Atrophy, Juvenile, Proximal, Autosomal Dominant 58
Autosomal Dominant Childhood Proximal Spinal Muscular Atrophy 76
Autosomal Dominant Juvenile Proximal Spinal Muscular Atrophy 76
Kugelberg-Welander Syndrome, Autosomal Dominant 58
Autosomal Dominant Kugelberg-Welander Syndrome 76
Sma-Led1 54
Sma-Led 76
Smaled 58

Characteristics:

Orphanet epidemiological data:

60
dync1h1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: adult;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
onset in early childhood
non-progressive or very slowly progressive


HPO:

33
spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant:
Onset and clinical course childhood onset slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

OMIM 58 158600
MeSH 45 D009134
ICD10 via Orphanet 35 G12.1
UMLS via Orphanet 75 C1834690
Orphanet 60 ORPHA209341
MedGen 43 C1834690
UMLS 74 C1834690

Summaries for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

OMIM : 58 Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (Harms et al., 2010). The most common form of SMA (see, e.g., SMA1, 253300) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (600354) on chromosome 5q. (158600)

MalaCards based summary : Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant, also known as smaled1, is related to spinal muscular atrophy with lower extremity predominance and autosomal dominant childhood-onset proximal spinal muscular atrophy, and has symptoms including waddling gait An important gene associated with Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant is DYNC1H1 (Dynein Cytoplasmic 1 Heavy Chain 1). Affiliated tissues include spinal cord, and related phenotypes are global developmental delay and abnormality of the foot

UniProtKB/Swiss-Prot : 76 Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant: A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMALED1 is characterized by muscle weakness predominantly affecting the proximal lower extremities.

Related Diseases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:



Diseases related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant

Symptoms & Phenotypes for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Human phenotypes related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

33 (show all 12)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 33 occasional (7.5%) HP:0001263
2 abnormality of the foot 33 HP:0001760
3 waddling gait 33 HP:0002515
4 proximal lower limb amyotrophy 33 HP:0008956
5 proximal muscle weakness in lower limbs 33 HP:0008994
6 difficulty running 33 HP:0009046
7 sensory impairment 33 HP:0003474
8 emg: neuropathic changes 33 HP:0003445
9 spinal muscular atrophy 33 HP:0007269
10 decreased patellar reflex 33 HP:0011808
11 delayed ability to walk 33 HP:0031936
12 type 2 muscle fiber predominance 33 HP:0010602

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
waddling gait
delayed walking
difficulty running and climbing stairs
muscle weakness, symmetric, proximal due to motor neuronopathy
cognitive delay, mild (1 patient)

Muscle Soft Tissue:
muscle weakness, symmetric, proximal, lower limbs
muscle atrophy, lower limbs
hip abductor weakness and atrophy
type 2 muscle fiber predominance
emg shows chronic denervation

Skeletal Feet:
foot deformities (variable)

Neurologic Peripheral Nervous System:
decreased patellar reflexes
no sensory impairment

Clinical features from OMIM:

158600

UMLS symptoms related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:


waddling gait

Drugs & Therapeutics for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant

Genetic Tests for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Genetic tests related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Spinal Muscular Atrophy, Lower Extremity Predominant 1, Autosomal Dominant 30 DYNC1H1

Anatomical Context for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

MalaCards organs/tissues related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

42
Spinal Cord

Publications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Articles related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

# Title Authors Year
1
Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations. ( 26998597 )
2016
2
A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance. ( 22847149 )
2012
3
Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. ( 22459677 )
2012
4
Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. ( 21820100 )
2011
5
Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32. ( 20697106 )
2010
6
A cytoplasmic dynein tail mutation impairs motor processivity. ( 21102439 )
2010
7
Mutations in dynein link motor neuron degeneration to defects in retrograde transport. ( 12730604 )
2003

Variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

76
# Symbol AA change Variation ID SNP ID
1 DYNC1H1 p.His306Arg VAR_066651 rs387906738
2 DYNC1H1 p.Ile584Leu VAR_067820 rs387906741
3 DYNC1H1 p.Lys671Glu VAR_067821 rs387906742
4 DYNC1H1 p.Tyr970Cys VAR_067822 rs387906743
5 DYNC1H1 p.Arg264Leu VAR_073156 rs713993043
6 DYNC1H1 p.Arg598Cys VAR_073157 rs587780564
7 DYNC1H1 p.Pro776Leu VAR_078241 rs105751808
8 DYNC1H1 p.Gly1132Glu VAR_078242

ClinVar genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

6 (show all 50)
# Gene Variation Type Significance SNP ID Assembly Location
1 DYNC1H1 NM_001376.4(DYNC1H1): c.917A> G (p.His306Arg) single nucleotide variant Pathogenic rs387906738 GRCh37 Chromosome 14, 102446843: 102446843
2 DYNC1H1 NM_001376.4(DYNC1H1): c.917A> G (p.His306Arg) single nucleotide variant Pathogenic rs387906738 GRCh38 Chromosome 14, 101980506: 101980506
3 DYNC1H1 NM_001376.4(DYNC1H1): c.1750A> C (p.Ile584Leu) single nucleotide variant Pathogenic rs387906741 GRCh37 Chromosome 14, 102452312: 102452312
4 DYNC1H1 NM_001376.4(DYNC1H1): c.1750A> C (p.Ile584Leu) single nucleotide variant Pathogenic rs387906741 GRCh38 Chromosome 14, 101985975: 101985975
5 DYNC1H1 NM_001376.4(DYNC1H1): c.2011A> G (p.Lys671Glu) single nucleotide variant Pathogenic rs387906742 GRCh37 Chromosome 14, 102452573: 102452573
6 DYNC1H1 NM_001376.4(DYNC1H1): c.2011A> G (p.Lys671Glu) single nucleotide variant Pathogenic rs387906742 GRCh38 Chromosome 14, 101986236: 101986236
7 DYNC1H1 NM_001376.4(DYNC1H1): c.2909A> G (p.Tyr970Cys) single nucleotide variant Pathogenic rs387906743 GRCh37 Chromosome 14, 102457904: 102457904
8 DYNC1H1 NM_001376.4(DYNC1H1): c.2909A> G (p.Tyr970Cys) single nucleotide variant Pathogenic rs387906743 GRCh38 Chromosome 14, 101991567: 101991567
9 DYNC1H1 NM_001376.5(DYNC1H1): c.1792C> T (p.Arg598Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587780564 GRCh37 Chromosome 14, 102452354: 102452354
10 DYNC1H1 NM_001376.5(DYNC1H1): c.1792C> T (p.Arg598Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587780564 GRCh38 Chromosome 14, 101986017: 101986017
11 DYNC1H1 NM_001376.4(DYNC1H1): c.3603G> T (p.Arg1201Ser) single nucleotide variant Pathogenic rs727505393 GRCh37 Chromosome 14, 102463410: 102463410
12 DYNC1H1 NM_001376.4(DYNC1H1): c.3603G> T (p.Arg1201Ser) single nucleotide variant Pathogenic rs727505393 GRCh38 Chromosome 14, 101997073: 101997073
13 DYNC1H1 NM_001376.4(DYNC1H1): c.5985C> T (p.Ala1995=) single nucleotide variant Conflicting interpretations of pathogenicity rs140841480 GRCh37 Chromosome 14, 102476187: 102476187
14 DYNC1H1 NM_001376.4(DYNC1H1): c.5985C> T (p.Ala1995=) single nucleotide variant Conflicting interpretations of pathogenicity rs140841480 GRCh38 Chromosome 14, 102009850: 102009850
15 DYNC1H1 NM_001376.4(DYNC1H1): c.7918G> A (p.Glu2640Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs797045535 GRCh37 Chromosome 14, 102483494: 102483494
16 DYNC1H1 NM_001376.4(DYNC1H1): c.7918G> A (p.Glu2640Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs797045535 GRCh38 Chromosome 14, 102017157: 102017157
17 DYNC1H1 NM_001376.4(DYNC1H1): c.2327C> T (p.Pro776Leu) single nucleotide variant Pathogenic rs1057518083 GRCh37 Chromosome 14, 102452889: 102452889
18 DYNC1H1 NM_001376.4(DYNC1H1): c.2327C> T (p.Pro776Leu) single nucleotide variant Pathogenic rs1057518083 GRCh38 Chromosome 14, 101986552: 101986552
19 DYNC1H1 NM_001376.4(DYNC1H1): c.5885G> A (p.Arg1962His) single nucleotide variant Likely pathogenic rs1057518287 GRCh37 Chromosome 14, 102474582: 102474582
20 DYNC1H1 NM_001376.4(DYNC1H1): c.5885G> A (p.Arg1962His) single nucleotide variant Likely pathogenic rs1057518287 GRCh38 Chromosome 14, 102008245: 102008245
21 DYNC1H1 NM_001376.4(DYNC1H1): c.12332A> G (p.Lys4111Arg) single nucleotide variant Uncertain significance rs1060499574 GRCh38 Chromosome 14, 102042440: 102042440
22 DYNC1H1 NM_001376.4(DYNC1H1): c.12332A> G (p.Lys4111Arg) single nucleotide variant Uncertain significance rs1060499574 GRCh37 Chromosome 14, 102508777: 102508777
23 DYNC1H1 NM_001376.4(DYNC1H1): c.9193G> A (p.Val3065Met) single nucleotide variant Uncertain significance rs377668381 GRCh37 Chromosome 14, 102494100: 102494100
24 DYNC1H1 NM_001376.4(DYNC1H1): c.9193G> A (p.Val3065Met) single nucleotide variant Uncertain significance rs377668381 GRCh38 Chromosome 14, 102027763: 102027763
25 DYNC1H1 NM_001376.4(DYNC1H1): c.2376C> T (p.Cys792=) single nucleotide variant Conflicting interpretations of pathogenicity rs35092963 GRCh37 Chromosome 14, 102452938: 102452938
26 DYNC1H1 NM_001376.4(DYNC1H1): c.2376C> T (p.Cys792=) single nucleotide variant Conflicting interpretations of pathogenicity rs35092963 GRCh38 Chromosome 14, 101986601: 101986601
27 DYNC1H1 NM_001376.4(DYNC1H1): c.3073C> T (p.Arg1025Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs777387819 GRCh37 Chromosome 14, 102460578: 102460578
28 DYNC1H1 NM_001376.4(DYNC1H1): c.3073C> T (p.Arg1025Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs777387819 GRCh38 Chromosome 14, 101994241: 101994241
29 DYNC1H1 NM_001376.4(DYNC1H1): c.13414G> A (p.Gly4472Ser) single nucleotide variant Uncertain significance rs199692678 GRCh37 Chromosome 14, 102515818: 102515818
30 DYNC1H1 NM_001376.4(DYNC1H1): c.13414G> A (p.Gly4472Ser) single nucleotide variant Uncertain significance rs199692678 GRCh38 Chromosome 14, 102049481: 102049481
31 DYNC1H1 NM_001376.4(DYNC1H1): c.13873G> A (p.Glu4625Lys) single nucleotide variant Uncertain significance rs200149883 GRCh37 Chromosome 14, 102516832: 102516832
32 DYNC1H1 NM_001376.4(DYNC1H1): c.13873G> A (p.Glu4625Lys) single nucleotide variant Uncertain significance rs200149883 GRCh38 Chromosome 14, 102050495: 102050495
33 DYNC1H1 NM_001376.4(DYNC1H1): c.10354G> A (p.Ala3452Thr) single nucleotide variant Uncertain significance rs1555411400 GRCh37 Chromosome 14, 102499762: 102499762
34 DYNC1H1 NM_001376.4(DYNC1H1): c.10354G> A (p.Ala3452Thr) single nucleotide variant Uncertain significance rs1555411400 GRCh38 Chromosome 14, 102033425: 102033425
35 DYNC1H1 NM_001376.4(DYNC1H1): c.1817C> T (p.Thr606Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102452379: 102452379
36 DYNC1H1 NM_001376.4(DYNC1H1): c.1817C> T (p.Thr606Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 101986042: 101986042
37 DYNC1H1 NM_001376.4(DYNC1H1): c.9607G> A (p.Val3203Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102496014: 102496014
38 DYNC1H1 NM_001376.4(DYNC1H1): c.9607G> A (p.Val3203Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102029677: 102029677
39 DYNC1H1 NM_001376.5(DYNC1H1): c.915A> G (p.Lys305=) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102446841: 102446841
40 DYNC1H1 NM_001376.5(DYNC1H1): c.915A> G (p.Lys305=) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 101980504: 101980504
41 DYNC1H1 NM_001376.5(DYNC1H1): c.11806G> A (p.Val3936Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102506688: 102506688
42 DYNC1H1 NM_001376.5(DYNC1H1): c.11806G> A (p.Val3936Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102040351: 102040351
43 DYNC1H1 NM_001376.5(DYNC1H1): c.12084C> G (p.Thr4028=) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102508053: 102508053
44 DYNC1H1 NM_001376.5(DYNC1H1): c.12084C> G (p.Thr4028=) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102041716: 102041716
45 DYNC1H1 NM_001376.5(DYNC1H1): c.12192G> A (p.Thr4064=) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102508439: 102508439
46 DYNC1H1 NM_001376.5(DYNC1H1): c.12192G> A (p.Thr4064=) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102042102: 102042102
47 DYNC1H1 NM_001376.5(DYNC1H1): c.13483G> A (p.Ala4495Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102515887: 102515887
48 DYNC1H1 NM_001376.5(DYNC1H1): c.13483G> A (p.Ala4495Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102049550: 102049550
49 DYNC1H1 NM_001376.5(DYNC1H1): c.13497T> C (p.Gly4499=) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 102515901: 102515901
50 DYNC1H1 NM_001376.5(DYNC1H1): c.13497T> C (p.Gly4499=) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 102049564: 102049564

Expression for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

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