XFEPS
MCID: XFP001
MIFTS: 45

Xfe Progeroid Syndrome (XFEPS)

Categories: Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Xfe Progeroid Syndrome

MalaCards integrated aliases for Xfe Progeroid Syndrome:

Name: Xfe Progeroid Syndrome 56 12 52 73 29 13 6 43 15 71
Xpf-Ercc1 Progeroid Syndrome 56 12 52 73
Xfeps 56 12 73
Progeroid Syndrome, Xfe 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
based on a report of a 15-year-old boy of consanguineous afghan parents (last curated february 2019)
death at age 16


HPO:

31
xfe progeroid syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Xfe Progeroid Syndrome

UniProtKB/Swiss-Prot : 73 XFE progeroid syndrome: A syndrome characterized by aged bird-like facies, lack of subcutaneous fat, dwarfism, cachexia and microcephaly. Additional features include sun-sensitivity from birth, learning disabilities, hearing loss, and visual impairment.

MalaCards based summary : Xfe Progeroid Syndrome, also known as xpf-ercc1 progeroid syndrome, is related to progeroid syndrome and cockayne syndrome type iii. An important gene associated with Xfe Progeroid Syndrome is ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit), and among its related pathways/superpathways are Transcription-Coupled Nucleotide Excision Repair (TC-NER) and Chks in Checkpoint Regulation. Affiliated tissues include skin, eye and liver, and related phenotypes are hearing impairment and prominent supraorbital ridges

Disease Ontology : 12 A syndrome that is characterized by aged bird-like facies, lack of subcutaneous fat, dwarfism, cachexia and microcephaly and that has material basis in homozygous mutation in the ERCC4 gene on chromosome 16p13.

More information from OMIM: 610965

Related Diseases for Xfe Progeroid Syndrome

Diseases in the Progeroid Syndrome family:

Xfe Progeroid Syndrome

Diseases related to Xfe Progeroid Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
# Related Disease Score Top Affiliating Genes
1 progeroid syndrome 10.2 WRN ERCC4
2 cockayne syndrome type iii 10.2 ERCC8 ERCC6
3 fanconi anemia, complementation group r 10.2 SLX4 ERCC6
4 fanconi anemia, complementation group o 10.2 SLX4 ERCC6
5 enophthalmos 10.2 ERCC8 ERCC6
6 fanconi anemia, complementation group t 10.1 SLX4 ERCC6
7 fanconi anemia, complementation group p 10.1 SLX4 ERCC6
8 fanconi anemia, complementation group n 10.1 SLX4 ERCC6
9 fanconi anemia, complementation group d1 10.0 SLX4 ERCC6
10 fanconi anemia, complementation group q 10.0 SLX4 ERCC6 ERCC4
11 skin atrophy 10.0 WRN ERCC6
12 cockayne syndrome b 10.0 ERCC8 ERCC6 ERCC1
13 xeroderma pigmentosum, complementation group e 9.9 XPA ERCC5
14 fanconi anemia, complementation group j 9.9 WRN SLX4 ERCC6
15 rothmund-thomson syndrome, type 2 9.8 WRN ERCC6
16 cerebrooculofacioskeletal syndrome 1 9.8 ERCC6 ERCC5 ERCC1
17 xeroderma pigmentosum-cockayne syndrome complex 9.7 ERCC5 ERCC4 ERCC3
18 trichothiodystrophy 4, nonphotosensitive 9.7 GTF2H5 ERCC3
19 xeroderma pigmentosum, complementation group a 9.7 XPA XAB2 ERCC6 ERCC1
20 autosomal genetic disease 9.7 XPA WRN ERCC6 ERCC1
21 xeroderma pigmentosum, complementation group c 9.7 XPA ERCC6 ERCC3 ERCC1
22 skin carcinoma 9.6 XPA ERCC6 ERCC3
23 acoustic neuroma 9.6 ERCC5 ERCC4
24 cerebro-oculo-facio-skeletal syndrome 9.3 ERCC6 ERCC5 ERCC4 ERCC3 ERCC1
25 hutchinson-gilford progeria syndrome 9.2 XPA WRN ERCC8 ERCC6 ERCC4 ERCC1
26 fanconi anemia, complementation group a 9.2 XPA WRN SLX4 ERCC6 ERCC4 ERCC1
27 robinow syndrome, autosomal recessive 1 9.1 XPA UVSSA GTF2H5 ERCC8 ERCC6
28 cockayne syndrome a 9.0 ERCC8 ERCC6 ERCC5 ERCC4 ERCC3 ERCC1
29 xeroderma pigmentosum, complementation group f 8.8 XPA SLX4 ERCC6 ERCC5 ERCC4 ERCC3
30 autosomal recessive disease 8.7 XPA WRN GTF2H5 ERCC6 ERCC3 ERCC1
31 trichothiodystrophy 8.4 XPA GTF2H5 ERCC6 ERCC5 ERCC4 ERCC3
32 cockayne syndrome 8.1 XPA XAB2 UVSSA ERCC8 ERCC6 ERCC5
33 xeroderma pigmentosum group e 7.9 XPA UVSSA GTF2H5 ERCC8 ERCC6 ERCC5
34 xeroderma pigmentosum, complementation group g 7.9 XPA UVSSA GTF2H5 ERCC8 ERCC6 ERCC5
35 xeroderma pigmentosum, complementation group d 7.8 XPA WRN GTF2H5 ERCC8 ERCC6 ERCC5
36 xeroderma pigmentosum, complementation group b 7.5 XPA WRN UVSSA GTF2H5 ERCC8 ERCC6
37 trichothiodystrophy 1, photosensitive 7.5 XPA WRN UVSSA GTF2H5 ERCC8 ERCC6
38 uv-sensitive syndrome 7.5 XPA XAB2 UVSSA GTF2H5 ERCC8 ERCC6
39 xeroderma pigmentosum, variant type 6.8 XPA XAB2 WRN UVSSA SLX4 GTF2H5

Graphical network of the top 20 diseases related to Xfe Progeroid Syndrome:



Diseases related to Xfe Progeroid Syndrome

Symptoms & Phenotypes for Xfe Progeroid Syndrome

Human phenotypes related to Xfe Progeroid Syndrome:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 HP:0000365
2 prominent supraorbital ridges 31 HP:0000336
3 scoliosis 31 HP:0002650
4 microcephaly 31 HP:0000252
5 visual impairment 31 HP:0000505
6 optic atrophy 31 HP:0000648
7 proteinuria 31 HP:0000093
8 renal insufficiency 31 HP:0000083
9 intellectual disability, mild 31 HP:0001256
10 dry skin 31 HP:0000958
11 ascites 31 HP:0001541
12 cachexia 31 HP:0004326
13 hypertension 31 HP:0000822
14 elevated hepatic transaminase 31 HP:0002910
15 narrow face 31 HP:0000275
16 prematurely aged appearance 31 HP:0007495
17 deeply set eye 31 HP:0000490
18 ventriculomegaly 31 HP:0002119
19 convex nasal ridge 31 HP:0000444
20 high pitched voice 31 HP:0001620
21 severe short stature 31 HP:0003510
22 hypoplasia of dental enamel 31 HP:0006297
23 dermal atrophy 31 HP:0004334
24 absence of subcutaneous fat 31 HP:0007485
25 poor coordination 31 HP:0002370

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
hearing impairment

Head And Neck Eyes:
optic atrophy
no cataracts
sunken orbits

Skin Nails Hair Skin:
dry skin
atrophic skin
no evidence of skin cancer

Cardiovascular Vascular:
hypertension

Neurologic Central Nervous System:
enlarged ventricles
hypotonic
learning disability, mild

Head And Neck Nose:
beaked nose

Growth Height:
short stature (-7 sd at age 15)

Head And Neck Teeth:
enamel dysplasia without caries

Neoplasia:
no evidence of skin cancer

Laboratory Abnormalities:
fibroblasts showed reduced levels of uv_induced dna damage repair (~5% normal)

Skeletal Spine:
scoliosis

Genitourinary Kidneys:
proteinuria
renal insufficiency, severe

Abdomen External Features:
ascites

Head And Neck Face:
narrow face
prominent brow
wizened appearance

Growth Weight:
normal birth weight
weight loss starting at age 12

Voice:
high-pitched voice

Head And Neck Head:
microcephaly (-5 sd)

Abdomen Liver:
abnormal serum liver enzymes, mild

Muscle Soft Tissue:
loss of subcutaneous fat

Clinical features from OMIM:

610965

GenomeRNAi Phenotypes related to Xfe Progeroid Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.84 ERCC4 ERCC5 ERCC6 XAB2
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.84 ERCC1 ERCC4 ERCC5 ERCC6 ERCC8
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.84 ERCC1 ERCC4 ERCC5 ERCC6 ERCC8 XAB2

MGI Mouse Phenotypes related to Xfe Progeroid Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.02 ERCC1 ERCC3 ERCC4 ERCC5 ERCC6 ERCC8
2 cellular MP:0005384 10.01 ERCC1 ERCC3 ERCC4 ERCC6 ERCC8 SLX4
3 homeostasis/metabolism MP:0005376 9.97 ERCC1 ERCC3 ERCC4 ERCC5 ERCC6 ERCC8
4 mortality/aging MP:0010768 9.9 ERCC1 ERCC3 ERCC4 ERCC5 ERCC6 ERCC8
5 integument MP:0010771 9.8 ERCC1 ERCC3 ERCC5 ERCC6 ERCC8 WRN
6 neoplasm MP:0002006 9.43 ERCC1 ERCC3 ERCC6 ERCC8 WRN XPA
7 vision/eye MP:0005391 9.1 ERCC1 ERCC6 ERCC8 SLX4 WRN XPA

Drugs & Therapeutics for Xfe Progeroid Syndrome

Search Clinical Trials , NIH Clinical Center for Xfe Progeroid Syndrome

Cochrane evidence based reviews: xfe progeroid syndrome

Genetic Tests for Xfe Progeroid Syndrome

Genetic tests related to Xfe Progeroid Syndrome:

# Genetic test Affiliating Genes
1 Xfe Progeroid Syndrome 29 ERCC4

Anatomical Context for Xfe Progeroid Syndrome

MalaCards organs/tissues related to Xfe Progeroid Syndrome:

40
Skin, Eye, Liver

Publications for Xfe Progeroid Syndrome

Articles related to Xfe Progeroid Syndrome:

# Title Authors PMID Year
1
ERCC4 variants identified in a cohort of patients with segmental progeroid syndromes. 56 6 61
29105242 2018
2
A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. 6 56
17183314 2006
3
Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxic stress. 61
23852002 2013
4
Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia. 61
23623386 2013
5
NF-κB inhibition delays DNA damage-induced senescence and aging in mice. 61
22706308 2012
6
Computational image analysis of nuclear morphology associated with various nuclear-specific aging disorders. 61
22127259 2011
7
Premature aging-related peripheral neuropathy in a mouse model of progeria. 61
21596054 2011
8
Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. 61
21612988 2011
9
Hyper telomere recombination accelerates replicative senescence and may promote premature aging. 61
20798040 2010
10
Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients. 61
20221251 2010

Variations for Xfe Progeroid Syndrome

ClinVar genetic disease variations for Xfe Progeroid Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ERCC4 NM_005236.2(ERCC4):c.458G>C (p.Arg153Pro)SNV Pathogenic 16581 rs121913050 16:14020487-14020487 16:13926630-13926630
2 ERCC4 NM_005236.2(ERCC4):c.1765C>T (p.Arg589Trp)SNV Pathogenic/Likely pathogenic 55829 rs147105770 16:14029554-14029554 16:13935697-13935697
3 ERCC4 NM_005236.2(ERCC4):c.388+1164_792+795deldeletion Pathogenic/Likely pathogenic 625138
4 ERCC4 NM_005236.3(ERCC4):c.2395C>T (p.Arg799Trp)SNV Conflicting interpretations of pathogenicity 16580 rs121913049 16:14041848-14041848 16:13947991-13947991
5 ERCC4 NM_005236.2(ERCC4):c.1563C>G (p.Ser521Arg)SNV Conflicting interpretations of pathogenicity 134153 rs41552412 16:14029352-14029352 16:13935495-13935495

UniProtKB/Swiss-Prot genetic disease variations for Xfe Progeroid Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 ERCC4 p.Arg153Pro VAR_034802 rs121913050

Expression for Xfe Progeroid Syndrome

Search GEO for disease gene expression data for Xfe Progeroid Syndrome.

Pathways for Xfe Progeroid Syndrome

Pathways related to Xfe Progeroid Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.59 XPA XAB2 UVSSA GTF2H5 ERCC8 ERCC6
2
Show member pathways
12.53 XPA XAB2 ERCC8 ERCC6 ERCC5 ERCC4
3
Show member pathways
12.4 XPA XAB2 WRN UVSSA SLX4 GTF2H5
4 12.24 XPA WRN ERCC4 ERCC3 ERCC1
5
Show member pathways
12 WRN SLX4 ERCC4 ERCC1
6
Show member pathways
11.68 GTF2H5 ERCC6 ERCC3
7
Show member pathways
11.62 XPA GTF2H5 ERCC8 ERCC6 ERCC5 ERCC4
8 11.58 SLX4 ERCC4 ERCC1
9 11.39 XPA GTF2H5 ERCC3
10 11.12 XPA ERCC6 ERCC4 ERCC3 ERCC1
11
Show member pathways
10.99 ERCC4 ERCC1

GO Terms for Xfe Progeroid Syndrome

Cellular components related to Xfe Progeroid Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.06 XPA XAB2 WRN SLX4 GTF2H5 ERCC8
2 nucleoplasm GO:0005654 9.73 XPA XAB2 WRN UVSSA SLX4 GTF2H5
3 nuclear chromosome, telomeric region GO:0000784 9.63 SLX4 ERCC4 ERCC1
4 chromosome, telomeric region GO:0000781 9.54 WRN SLX4 ERCC4
5 DNA replication factor A complex GO:0005662 9.48 XPA ERCC5
6 transcription factor TFIIH holo complex GO:0005675 9.43 GTF2H5 ERCC3
7 ERCC4-ERCC1 complex GO:0070522 9.43 SLX4 ERCC4 ERCC1
8 transcription factor TFIIH core complex GO:0000439 9.4 GTF2H5 ERCC3
9 nucleotide-excision repair factor 1 complex GO:0000110 9.33 XPA ERCC4 ERCC1
10 nucleotide-excision repair complex GO:0000109 8.92 ERCC8 ERCC5 ERCC4 ERCC1

Biological processes related to Xfe Progeroid Syndrome according to GeneCards Suite gene sharing:

(show all 47)
# Name GO ID Score Top Affiliating Genes
1 response to oxidative stress GO:0006979 9.99 XPA WRN ERCC8 ERCC6 ERCC3 ERCC1
2 nucleotide-excision repair, DNA incision GO:0033683 9.93 XPA GTF2H5 ERCC5 ERCC4 ERCC3 ERCC1
3 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006296 9.91 XPA GTF2H5 ERCC5 ERCC4 ERCC3 ERCC1
4 global genome nucleotide-excision repair GO:0070911 9.89 XPA GTF2H5 ERCC4 ERCC3 ERCC1
5 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.88 WRN ERCC5 ERCC4 ERCC1
6 UV protection GO:0009650 9.88 XPA ERCC5 ERCC4 ERCC3 ERCC1
7 nucleotide-excision repair, DNA incision, 3'-to lesion GO:0006295 9.88 XPA GTF2H5 ERCC5 ERCC4 ERCC3 ERCC1
8 response to UV GO:0009411 9.87 XPA UVSSA ERCC8 ERCC6 ERCC5 ERCC4
9 DNA duplex unwinding GO:0032508 9.86 WRN ERCC8 ERCC6 ERCC3
10 nucleotide-excision repair GO:0006289 9.86 XPA SLX4 GTF2H5 ERCC8 ERCC5 ERCC4
11 DNA recombination GO:0006310 9.85 WRN SLX4 ERCC1
12 nucleotide-excision repair, preincision complex stabilization GO:0006293 9.85 XPA GTF2H5 ERCC5 ERCC4 ERCC3 ERCC1
13 transcription-coupled nucleotide-excision repair GO:0006283 9.85 XPA XAB2 UVSSA GTF2H5 ERCC8 ERCC6
14 multicellular organism growth GO:0035264 9.83 XPA ERCC6 ERCC1
15 nucleotide-excision repair, preincision complex assembly GO:0006294 9.83 XPA GTF2H5 ERCC5 ERCC3
16 double-strand break repair via homologous recombination GO:0000724 9.82 WRN SLX4 ERCC4
17 interstrand cross-link repair GO:0036297 9.81 SLX4 ERCC4 ERCC1
18 base-excision repair GO:0006284 9.78 XPA WRN ERCC6
19 transcription elongation from RNA polymerase I promoter GO:0006362 9.77 GTF2H5 ERCC6 ERCC3
20 nucleotide-excision repair, DNA duplex unwinding GO:0000717 9.75 XPA GTF2H5 ERCC3
21 response to X-ray GO:0010165 9.74 ERCC8 ERCC6 ERCC1
22 cellular response to DNA damage stimulus GO:0006974 9.73 XPA XAB2 WRN UVSSA SLX4 GTF2H5
23 positive regulation of transcription initiation from RNA polymerase II promoter GO:0060261 9.72 XPA ERCC6 ERCC1
24 t-circle formation GO:0090656 9.71 WRN SLX4 ERCC1
25 telomere maintenance GO:0000723 9.7 WRN ERCC4
26 embryonic organ development GO:0048568 9.7 ERCC3 ERCC1
27 transcription initiation from RNA polymerase I promoter GO:0006361 9.7 GTF2H5 ERCC3
28 7-methylguanosine mRNA capping GO:0006370 9.69 GTF2H5 ERCC3
29 positive regulation of DNA repair GO:0045739 9.69 ERCC8 ERCC6
30 termination of RNA polymerase I transcription GO:0006363 9.69 GTF2H5 ERCC3
31 cellular response to gamma radiation GO:0071480 9.68 WRN GTF2H5
32 multicellular organism aging GO:0010259 9.68 WRN ERCC1
33 resolution of meiotic recombination intermediates GO:0000712 9.68 SLX4 ERCC4
34 response to auditory stimulus GO:0010996 9.68 XPA ERCC8
35 single strand break repair GO:0000012 9.67 ERCC8 ERCC6
36 UV-damage excision repair GO:0070914 9.67 XPA ERCC1
37 negative regulation of telomere maintenance via telomere lengthening GO:1904357 9.66 SLX4 ERCC4
38 response to UV-C GO:0010225 9.66 WRN ERCC5
39 telomeric D-loop disassembly GO:0061820 9.65 WRN SLX4
40 double-strand break repair via classical nonhomologous end joining GO:0097680 9.64 ERCC8 ERCC6
41 replicative cell aging GO:0001302 9.64 WRN ERCC1
42 positive regulation of t-circle formation GO:1904431 9.63 SLX4 ERCC1
43 negative regulation of telomere maintenance GO:0032205 9.62 ERCC4 ERCC1
44 negative regulation of protection from non-homologous end joining at telomere GO:1905765 9.62 ERCC4 ERCC1
45 telomeric DNA-containing double minutes formation GO:0061819 9.61 ERCC4 ERCC1
46 nucleotide-excision repair involved in interstrand cross-link repair GO:1901255 9.6 XPA ERCC4
47 DNA repair GO:0006281 9.4 XPA XAB2 WRN UVSSA SLX4 GTF2H5

Molecular functions related to Xfe Progeroid Syndrome according to GeneCards Suite gene sharing:

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.36 XPA XAB2 WRN UVSSA SLX4 GTF2H5
2 DNA binding GO:0003677 10.1 XPA WRN ERCC6 ERCC5 ERCC4 ERCC3
3 hydrolase activity GO:0016787 10.07 WRN ERCC6 ERCC5 ERCC4 ERCC3 ERCC1
4 protein-containing complex binding GO:0044877 9.87 WRN ERCC8 ERCC6 ERCC5
5 helicase activity GO:0004386 9.75 WRN ERCC6 ERCC3
6 protein C-terminus binding GO:0008022 9.71 ERCC6 ERCC4 ERCC3 ERCC1
7 single-stranded DNA binding GO:0003697 9.7 ERCC5 ERCC4 ERCC1
8 endonuclease activity GO:0004519 9.67 ERCC5 ERCC4 ERCC1
9 promoter-specific chromatin binding GO:1990841 9.61 ERCC4 ERCC3 ERCC1
10 RNA polymerase II complex binding GO:0000993 9.6 UVSSA ERCC5
11 nuclease activity GO:0004518 9.56 WRN ERCC5 ERCC4 ERCC1
12 3'-5' DNA helicase activity GO:0043138 9.55 WRN ERCC3
13 endodeoxyribonuclease activity GO:0004520 9.54 ERCC5 ERCC4
14 DNA-dependent ATPase activity GO:0008094 9.54 ERCC8 ERCC6 ERCC3
15 TFIID-class transcription factor complex binding GO:0001094 9.51 ERCC4 ERCC1
16 single-stranded DNA endodeoxyribonuclease activity GO:0000014 9.48 ERCC4 ERCC1
17 bubble DNA binding GO:0000405 9.46 WRN ERCC5
18 protein N-terminus binding GO:0047485 9.46 ERCC6 ERCC5 ERCC4 ERCC3
19 3' overhang single-stranded DNA endodeoxyribonuclease activity GO:1990599 9.32 ERCC4 ERCC1
20 DNA helicase activity GO:0003678 9.26 WRN ERCC8 ERCC6 ERCC3
21 damaged DNA binding GO:0003684 8.92 XPA ERCC4 ERCC3 ERCC1

Sources for Xfe Progeroid Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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