RJALS
MCID: RJS001
MIFTS: 47

Ruijs-Aalfs Syndrome (RJALS)

Categories: Bone diseases, Cancer diseases, Fetal diseases, Genetic diseases, Liver diseases, Rare diseases

Aliases & Classifications for Ruijs-Aalfs Syndrome

MalaCards integrated aliases for Ruijs-Aalfs Syndrome:

Name: Ruijs-Aalfs Syndrome 57 12 58 72 36 29 6 15 39 70
Progeroid Features-Hepatocellular Carcinoma Predisposition Syndrome 12 58
Rjals 57 72

Characteristics:

Orphanet epidemiological data:

58
progeroid features-hepatocellular carcinoma predisposition syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: adolescent;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
based on 3 patients from 2 families (last curated january 2015)


HPO:

31
ruijs-aalfs syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Ruijs-Aalfs Syndrome

OMIM® : 57 Ruijs et al. (2003) reported a Moroccan boy with a chromosomal breakage who died of hepatocellular carcinoma at age 17 years. The boy was noted to have growth retardation at age 3 years; at age 7 he was found to have thoracic kyphosis, frontal bossing, and a delayed bone age of approximately 3 years. He underwent surgery for severe bilateral posterior subcapsular cataracts at age 14. Examination at age 15 showed short stature and low weight, with premature graying of scalp hair, small frontotemporal diameter, small deep-set eyes, bulbous nose with high nasal bridge, small upper lip, and micrognathia. In addition, he had thoracic kyphoscoliosis, sloping shoulders, mild pectus excavatum, moderate bilateral contractures of both elbows, bilateral clinodactyly, and pes planus. At age 17, he developed abdominal pain, and ultrasonography revealed a liver mass; biopsy confirmed hepatocellular carcinoma. Because of the advanced stage, no treatment was possible, and he died 2 months later. Although his parents were not known to be consanguineous, they originated from the same small Moroccan village. Lessel et al. (2014) studied 2 brothers from a nonconsanguineous Australian family of European ancestry who exhibited low body weight, micrognathia, triangular face, muscular atrophy, lipodystrophy, bilateral simian creases, delayed bone age, and mild joint restrictions in the fingers and elbows. In addition, both brothers developed early-onset hepatocellular carcinoma, at ages 16 and 14 years, respectively. The older brother died at age 18 from complications of acute fulminant hepatic failure. Analysis of patient tumor biopsies showed strong focal accumulations of cancer biomarkers as well as a high proliferative index compared to healthy liver or to cells from idiopathic hepatocellular carcinoma. (616200) (Updated 20-May-2021)

MalaCards based summary : Ruijs-Aalfs Syndrome, also known as progeroid features-hepatocellular carcinoma predisposition syndrome, is related to spinocerebellar ataxia, autosomal recessive 23 and spinocerebellar ataxia type 1 with axonal neuropathy. An important gene associated with Ruijs-Aalfs Syndrome is SPRTN (SprT-Like N-Terminal Domain), and among its related pathways/superpathways are DNA Double-Strand Break Repair and DNA Damage. Affiliated tissues include liver, skeletal muscle and bone, and related phenotypes are frontal bossing and delayed skeletal maturation

Disease Ontology : 12 A syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma that has material basis in homozygous or compound heterozygous mutation in SPRTN on 1q42.2.

KEGG : 36 Ruijs-Aalfs syndrome is characterized by early onset hepatocellular carcinoma, genomic instability and progeroid features. It has been reported that mutations in SPRTN cause this disease.

UniProtKB/Swiss-Prot : 72 Ruijs-Aalfs syndrome: A syndrome characterized by genomic instability, progeroid features, and susceptibility toward early onset hepatocellular carcinoma.

Wikipedia : 73 Ruijs-Aalfs syndrome is a rare condition characterised by facial and skeletal abnormalities along with... more...

Related Diseases for Ruijs-Aalfs Syndrome

Graphical network of the top 20 diseases related to Ruijs-Aalfs Syndrome:



Diseases related to Ruijs-Aalfs Syndrome

Symptoms & Phenotypes for Ruijs-Aalfs Syndrome

Human phenotypes related to Ruijs-Aalfs Syndrome:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 31 HP:0002007
2 delayed skeletal maturation 31 HP:0002750
3 pes planus 31 HP:0001763
4 short stature 31 HP:0004322
5 skeletal muscle atrophy 31 HP:0003202
6 micrognathia 31 HP:0000347
7 pectus excavatum 31 HP:0000767
8 elbow flexion contracture 31 HP:0002987
9 lipodystrophy 31 HP:0009125
10 prominent nasal bridge 31 HP:0000426
11 bulbous nose 31 HP:0000414
12 down-sloping shoulders 31 HP:0200021
13 decreased body weight 31 HP:0004325
14 triangular face 31 HP:0000325
15 clinodactyly 31 HP:0030084
16 thoracic kyphoscoliosis 31 HP:0005659
17 hepatocellular carcinoma 31 HP:0001402
18 posterior subcapsular cataract 31 HP:0007787

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
frontal bossing
small frontotemporal diameter

Growth Height:
short stature

Muscle Soft Tissue:
lipodystrophy
muscular atrophy

Skeletal Spine:
thoracic kyphoscoliosis

Skeletal:
delayed bone age

Chest External Features:
sloping shoulders

Head And Neck Mouth:
small upper lip

Head And Neck Eyes:
small deep-set eyes
posterior subcapsular cataract, bilateral

Skin Nails Hair Skin:
bilateral palmar simian creases

Neoplasia:
early-onset hepatocellular carcinoma
sensitivity to genotoxic agents

Skeletal Feet:
pes planus

Head And Neck Face:
micrognathia
triangular face

Head And Neck Nose:
bulbous nose
high nasal bridge

Abdomen Liver:
hepatocellular carcinoma

Growth Weight:
low weight

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum, mild

Skeletal Limbs:
contractures of elbows

Skeletal Hands:
bilateral clinodactyly
joint restrictions of fingers, mild

Skin Nails Hair Hair:
premature graying of scalp hair

Laboratory Abnormalities:
structural abnormalities seen on chromosome analysis
elevated urinary hyaluronic acid levels

Clinical features from OMIM®:

616200 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Ruijs-Aalfs Syndrome according to GeneCards Suite gene sharing:

26 (show all 22)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.68 H2AC18
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-118 9.68 NR0B2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.68 NR0B2
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-124 9.68 TRAIP
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.68 H2AC18
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 9.68 NR0B2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-147 9.68 TRAIP
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 9.68 TRAIP
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-151 9.68 NR0B2
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.68 H2AC18
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-167 9.68 NR0B2
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.68 H2AC18
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-2 9.68 TRAIP
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 9.68 TRAIP
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.68 H2AC18
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.68 H2AC18
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 9.68 H2AC18
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-70 9.68 NR0B2
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 9.68 NR0B2 TRAIP
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.68 NR0B2
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.68 TRAIP
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-9 9.68 NR0B2

Drugs & Therapeutics for Ruijs-Aalfs Syndrome

Search Clinical Trials , NIH Clinical Center for Ruijs-Aalfs Syndrome

Genetic Tests for Ruijs-Aalfs Syndrome

Genetic tests related to Ruijs-Aalfs Syndrome:

# Genetic test Affiliating Genes
1 Ruijs-Aalfs Syndrome 29 SPRTN

Anatomical Context for Ruijs-Aalfs Syndrome

MalaCards organs/tissues related to Ruijs-Aalfs Syndrome:

40
Liver, Skeletal Muscle, Bone

Publications for Ruijs-Aalfs Syndrome

Articles related to Ruijs-Aalfs Syndrome:

# Title Authors PMID Year
1
Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. 57 6
25261934 2014
2
Atypical progeroid syndrome: an unknown helicase gene defect? 57 6
12503110 2003
3
Structural Insight into DNA-Dependent Activation of Human Metalloprotease Spartan. 61
30893605 2019
4
Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis. 61
28199696 2017
5
SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks. 61
27852435 2016
6
Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN. 61
27871365 2016
7
Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair. 61
27871366 2016

Variations for Ruijs-Aalfs Syndrome

ClinVar genetic disease variations for Ruijs-Aalfs Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SPRTN NM_032018.7(SPRTN):c.723del (p.Lys241fs) Deletion Pathogenic 162628 rs527236212 GRCh37: 1:231488358-231488358
GRCh38: 1:231352612-231352612
2 SPRTN NM_032018.7(SPRTN):c.350A>G (p.Tyr117Cys) SNV Pathogenic 143916 rs527236213 GRCh37: 1:231483571-231483571
GRCh38: 1:231347825-231347825
3 SPRTN NM_032018.7(SPRTN):c.718_718+3del Deletion Pathogenic 143915 rs587593493 GRCh37: 1:231487316-231487319
GRCh38: 1:231351571-231351574

UniProtKB/Swiss-Prot genetic disease variations for Ruijs-Aalfs Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 SPRTN p.Tyr117Cys VAR_072708 rs527236213

Cosmic variations for Ruijs-Aalfs Syndrome:

9 (show top 50) (show all 15388)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM97724722 ZXDB liver,NS,carcinoma,hepatocellular carcinoma c.1308C>A p.D436E 23:57593356-57593356 3
2 COSM94430614 ZSWIM1 liver,NS,carcinoma,hepatocellular carcinoma c.1399A>C p.S467R 20:45883991-45883991 3
3 COSM94436083 ZSWIM1 liver,NS,carcinoma,hepatocellular carcinoma c.1399A>C p.S467R 20:45883991-45883991 3
4 COSM94063771 ZSCAN20 liver,NS,carcinoma,hepatocellular carcinoma c.2314G>T p.G772W 1:33494658-33494658 3
5 COSM88264637 ZRSR2 liver,NS,carcinoma,hepatocellular carcinoma c.304G>T p.E102* 23:15803788-15803788 3
6 COSM102741209 ZNRF3 liver,NS,carcinoma,hepatocellular carcinoma c.859A>G p.M287V 22:29049340-29049340 3
7 COSM131494492 ZNRF3 liver,NS,carcinoma,hepatocellular carcinoma c.1159A>G p.M387V 22:29049340-29049340 3
8 COSM103081572 ZNRF3 liver,NS,carcinoma,hepatocellular carcinoma c.859A>G p.M287V 22:29049340-29049340 3
9 COSM95977701 ZNFX1 liver,NS,carcinoma,hepatocellular carcinoma c.2580G>A p.L860= 20:49257501-49257501 3
10 COSM102131817 ZNFX1 liver,NS,carcinoma,hepatocellular carcinoma c.2580G>A p.L860= 20:49257501-49257501 3
11 COSM95960776 ZNFX1 liver,NS,carcinoma,hepatocellular carcinoma c.2580G>A p.L860= 20:49257501-49257501 3
12 COSM113317148 ZNF853 liver,NS,carcinoma,hepatocellular carcinoma c.1610G>T p.G537V 7:6622601-6622601 3
13 COSM99592496 ZNF829 liver,NS,carcinoma,hepatocellular carcinoma c.829T>A p.F277I 19:36891962-36891962 3
14 COSM128686611 ZNF829 liver,NS,carcinoma,hepatocellular carcinoma c.1072T>A p.F358I 19:36891962-36891962 3
15 COSM123358576 ZNF827 liver,NS,carcinoma,hepatocellular carcinoma c.691C>T p.L231= 4:145885684-145885684 3
16 COSM123949383 ZNF827 liver,NS,carcinoma,hepatocellular carcinoma c.1741C>T p.L581= 4:145885684-145885684 3
17 COSM101741672 ZNF827 liver,NS,carcinoma,hepatocellular carcinoma c.1741C>T p.L581= 4:145885684-145885684 3
18 COSM86004822 ZNF653 liver,NS,carcinoma,hepatocellular carcinoma c.1553A>C p.H518P 19:11485673-11485673 3
19 COSM98561269 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
20 COSM142353152 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
21 COSM142221290 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
22 COSM99854658 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.156G>A p.V52= 19:52002156-52002156 3
23 COSM139729931 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
24 COSM141470046 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
25 COSM141819438 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
26 COSM145038099 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 3
27 COSM91868668 ZNF536 liver,NS,carcinoma,hepatocellular carcinoma c.3900G>T p.K1300N 19:30557161-30557161 3
28 COSM91880764 ZNF536 liver,NS,carcinoma,hepatocellular carcinoma c.2171-78T>G p.? 19:30534769-30534769 3
29 COSM140721836 ZNF521 liver,NS,carcinoma,hepatocellular carcinoma c.2998+205G>A p.? 18:25194955-25194955 3
30 COSM131506983 ZNF521 liver,NS,carcinoma,hepatocellular carcinoma c.3658+205G>A p.? 18:25194955-25194955 3
31 COSM94799980 ZNF521 liver,NS,carcinoma,hepatocellular carcinoma c.3658+205G>A p.? 18:25194955-25194955 3
32 COSM90582798 ZNF518B liver,NS,carcinoma,hepatocellular carcinoma c.1624G>T p.E542* 4:10444705-10444705 3
33 COSM87577038 ZNF462 liver,NS,carcinoma,hepatocellular carcinoma c.6715G>T p.V2239L 9:106974156-106974156 3
34 COSM109096265 ZNF462 liver,NS,carcinoma,hepatocellular carcinoma c.3433G>T p.V1145L 9:106974156-106974156 3
35 COSM104985080 ZNF385B liver,NS,carcinoma,hepatocellular carcinoma c.298+23785G>T p.? 2:179745718-179745718 3
36 COSM104427909 ZNF385B liver,NS,carcinoma,hepatocellular carcinoma c.20G>T p.S7I 2:179745718-179745718 3
37 COSM151538615 ZNF385B liver,NS,carcinoma,hepatocellular carcinoma c.253+23785G>T p.? 2:179745718-179745718 3
38 COSM127708351 ZNF345 liver,NS,carcinoma,hepatocellular carcinoma c.47-856A>T p.? 19:36891962-36891962 3
39 COSM135887725 ZNF276 liver,NS,carcinoma,hepatocellular carcinoma c.1168C>G p.L390V 16:89734008-89734008 3
40 COSM84511025 ZNF276 liver,NS,carcinoma,hepatocellular carcinoma c.1219C>G p.L407V 16:89734008-89734008 3
41 COSM111609487 ZNF276 liver,NS,carcinoma,hepatocellular carcinoma c.1444C>G p.L482V 16:89734008-89734008 3
42 COSM92353291 ZNF26 liver,NS,carcinoma,hepatocellular carcinoma c.1010C>T p.T337I 12:133010889-133010889 3
43 COSM130415812 ZNF26 liver,NS,carcinoma,hepatocellular carcinoma c.950C>T p.T317I 12:133010889-133010889 3
44 COSM88697750 ZNF217 liver,NS,carcinoma,hepatocellular carcinoma c.*194A>T p.? 20:53569094-53569094 3
45 COSM95253159 ZNF217 liver,NS,carcinoma,hepatocellular carcinoma c.*194A>T p.? 20:53569094-53569094 3
46 COSM94505616 ZMYND12 liver,NS,carcinoma,hepatocellular carcinoma c.425-1G>T p.? 1:42440026-42440026 3
47 COSM89943752 ZMYM4 liver,NS,carcinoma,hepatocellular carcinoma c.86-8201G>T p.? 1:35350724-35350724 3
48 COSM101398456 ZIC2 liver,NS,carcinoma,hepatocellular carcinoma c.-18C>T p.? 13:99982047-99982047 3
49 COSM113521587 ZGPAT liver,NS,carcinoma,hepatocellular carcinoma c.*197C>A p.? 20:63736116-63736116 3
50 COSM94679661 ZGPAT liver,NS,carcinoma,hepatocellular carcinoma c.*197C>A p.? 20:63736116-63736116 3

Expression for Ruijs-Aalfs Syndrome

Search GEO for disease gene expression data for Ruijs-Aalfs Syndrome.

Pathways for Ruijs-Aalfs Syndrome

GO Terms for Ruijs-Aalfs Syndrome

Cellular components related to Ruijs-Aalfs Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome GO:0005694 9.65 WRN TRAIP TEX264 SPRTN H2AC18
2 nucleoplasm GO:0005654 9.65 ZNF451 WRN TRAIP TDP2 TDP1 SPRTN
3 nucleus GO:0005634 9.4 ZNF451 WRN TRAIP TEX264 TDP2 TDP1
4 replication fork GO:0005657 9.33 WRN TEX264 POLH

Biological processes related to Ruijs-Aalfs Syndrome according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 DNA replication GO:0006260 9.63 WRN POLH POLD3
2 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.58 WRN TDP2 TDP1
3 cellular response to DNA damage stimulus GO:0006974 9.56 WRN TRAIP TEX264 TDP2 TDP1 SPRTN
4 telomere maintenance GO:0000723 9.51 WRN POLD3
5 double-strand break repair GO:0006302 9.5 WRN TDP2 TDP1
6 DNA biosynthetic process GO:0071897 9.49 POLH POLD3
7 replication fork processing GO:0031297 9.48 WRN TRAIP
8 error-free translesion synthesis GO:0070987 9.43 SPRTN POLH
9 translesion synthesis GO:0019985 9.43 SPRTN POLH POLD3
10 response to UV-C GO:0010225 9.37 WRN POLH
11 DNA synthesis involved in DNA repair GO:0000731 9.33 WRN POLH POLD3
12 DNA repair GO:0006281 9.23 WRN TRAIP TEX264 TDP2 TDP1 SPRTN

Molecular functions related to Ruijs-Aalfs Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription corepressor activity GO:0003714 9.43 ZNF451 TDP2 NR0B2
2 exonuclease activity GO:0004527 9.32 WRN TDP1
3 DNA-directed DNA polymerase activity GO:0003887 9.16 POLH POLD3
4 nuclease activity GO:0004518 9.13 WRN TDP2 TDP1
5 single-stranded DNA binding GO:0003697 8.8 TDP2 TDP1 SPRTN

Sources for Ruijs-Aalfs Syndrome

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
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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