MCID: RHZ011
MIFTS: 49

Rhizomelic Chondrodysplasia Punctata, Type 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Bone diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for Rhizomelic Chondrodysplasia Punctata, Type 1

MalaCards integrated aliases for Rhizomelic Chondrodysplasia Punctata, Type 1:

Name: Rhizomelic Chondrodysplasia Punctata, Type 1 53 71 13 51 69
Rhizomelic Chondrodysplasia Punctata Type 1 12 23 49 55 28 14
Rcdp1 53 12 23 49 71
Peroxisome Biogenesis Disorder 9 53 12 71
Pbd9 53 12 71
Chondrodysplasia Punctata, Rhizomelic Form 53 71
Chondrodystrophia Calcificans Punctata 53 71
Cdpr 53 71
Chondrodysplasia Punctata, Rhizomelic Form; Cdpr 53
Peroxisome Biogenesis Disorder 9; Pbd9 53
Rhizomelic Chondrodysplasia Punctata 1 71
Chondrodysplasia Punctata, Rhizomelic 69

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
majority of children die before age 2


HPO:

31
rhizomelic chondrodysplasia punctata, type 1:
Inheritance autosomal recessive inheritance


GeneReviews:

23
Penetrance Penetrance is complete and the same for either sex...

Classifications:



Summaries for Rhizomelic Chondrodysplasia Punctata, Type 1

OMIM : 53 Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life. RCDP1 is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Individuals with RCDP1, carrying mutations in the PEX7 gene, have cells of peroxisome biogenesis disorder (PBD) complementation group 11 (CG11, equivalent to CGR). For information on the history of PBD complementation groups, see 214100. (215100)

MalaCards based summary : Rhizomelic Chondrodysplasia Punctata, Type 1, also known as rhizomelic chondrodysplasia punctata type 1, is related to chondrodysplasia punctata syndrome and rhizomelic chondrodysplasia punctata, and has symptoms including seizures, malar flattening and frontal bossing. An important gene associated with Rhizomelic Chondrodysplasia Punctata, Type 1 is PEX7 (Peroxisomal Biogenesis Factor 7), and among its related pathways/superpathways are Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways and Peroxisome. Affiliated tissues include bone and eye, and related phenotypes are growth/size/body region and homeostasis/metabolism

UniProtKB/Swiss-Prot : 71 Rhizomelic chondrodysplasia punctata 1: A peroxisome biogenesis disorder. It is characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe mental retardation with spasticity.

NIH Rare Diseases : 49 Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems. The condition is caused by mutations in the PEX7 gene. It is inherited in an autosomal recessive pattern. Rhizomelic chondrodysplasia punctata type 1 is one of five types of rhizomelic chondrodysplasia punctata. The types have similar features and are distinguished by their genetic cause. Last updated: 5/26/2015

Disease Ontology : 12 A rhizomelic chondrodysplasia punctata that has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the PEX7 gene on chromosome 6q23.3.

GeneReviews: NBK1270

Related Diseases for Rhizomelic Chondrodysplasia Punctata, Type 1

Diseases in the Rhizomelic Chondrodysplasia Punctata family:

Rhizomelic Chondrodysplasia Punctata, Type 1 Rhizomelic Chondrodysplasia Punctata, Type 2
Rhizomelic Chondrodysplasia Punctata, Type 3 Rhizomelic Chondrodysplasia Punctata, Type 5

Diseases related to Rhizomelic Chondrodysplasia Punctata, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 chondrodysplasia punctata syndrome 31.0 GNPAT PEX5 PEX7
2 rhizomelic chondrodysplasia punctata 30.4 AGPS GNPAT HADHB PEX5 PEX7 PHYH
3 neonatal respiratory failure 10.2
4 respiratory failure 10.2
5 human herpesvirus 8 10.0 IL6R RBFOX2
6 alpha-methylacyl-coa racemase deficiency 10.0 ACOX1 HSD17B4 PHYH SCP2
7 peroxisomal acyl-coa oxidase deficiency 9.9 ACOX1 HSD17B4 PEX5 SCP2
8 mulibrey nanism 9.9 PEX5 PEX7
9 d-bifunctional protein deficiency 9.8 ACOX1 HADHB HSD17B4 PEX5 SCP2
10 refsum disease, classic 9.6 GNPAT HSD17B4 PEX5 PEX7 PHYH SCP2
11 neonatal adrenoleukodystrophy 9.6 ACOX1 PEX12 PEX2 PEX5 PEX7 SCP2
12 zellweger syndrome 9.6 AGPS GNPAT PEX12 PEX2 PEX5
13 rhizomelic chondrodysplasia punctata, type 3 9.5 AGPS GNPAT PEX5 PEX7 UROD
14 peroxisomal biogenesis disorders 9.5 HSD17B4 PEX12 PEX2 PEX5 PEX7 PHEX
15 peroxisomal disease 9.2 AGPS GNPAT HADHB HSD17B4 PEX2 PEX5
16 rhizomelic chondrodysplasia punctata, type 5 9.2 AGPS FAR1 GNPAT PEX5 PEX5L PEX7
17 peroxisome biogenesis disorder 1b 9.1 GNPAT HSD17B4 PEX12 PEX2 PEX5 PEX7
18 rhizomelic chondrodysplasia punctata, type 2 8.1 AGPS FAR1 GNPAT PEX5 PEX5L PEX7

Graphical network of the top 20 diseases related to Rhizomelic Chondrodysplasia Punctata, Type 1:



Diseases related to Rhizomelic Chondrodysplasia Punctata, Type 1

Symptoms & Phenotypes for Rhizomelic Chondrodysplasia Punctata, Type 1

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
spasticity
mental retardation
cortical atrophy
severe delay in myelination

Respiratory Lung:
respiratory insufficiency

Skin Nails Hair Skin:
ichthyosis

Skin Nails Hair Hair:
alopecia

Skeletal Spine:
kyphoscoliosis
coronal cleft of vertebrae

Skeletal Limbs:
joint contractures
symmetrical rhizomelic limb shortening
metaphyseal splaying
epiphyseal calcification

Growth Height:
dwarfism

Skeletal:
calcific stippling of infantile cartilaginous skeleton
disappearance of stippling in first year of life

Head And Neck Face:
frontal bossing
micrognathia
flat face

Head And Neck Head:
microcephaly

Head And Neck Mouth:
cleft palate

Growth Other:
severe failure to thrive

Head And Neck Nose:
low nasal bridge

Head And Neck Ears:
sensorineural deafness

Head And Neck Eyes:
upward slanting palpebral fissures
congenital cataracts

Laboratory Abnormalities:
plasmalogen deficiency
acyl-coa:dihydroxyacetonephosphate acyltransferase deficiency
elevated plasma phytanic acid
unprocessed 3-oxoacyl coa thiolase


Clinical features from OMIM:

215100

Human phenotypes related to Rhizomelic Chondrodysplasia Punctata, Type 1:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 seizures 31 HP:0001250
2 malar flattening 31 HP:0000272
3 frontal bossing 31 HP:0002007
4 intellectual disability 31 HP:0001249
5 spasticity 31 HP:0001257
6 respiratory insufficiency 31 HP:0002093
7 depressed nasal bridge 31 HP:0005280
8 microcephaly 31 HP:0000252
9 sensorineural hearing impairment 31 HP:0000407
10 ichthyosis 31 HP:0008064
11 flexion contracture 31 HP:0001371
12 abnormality of metabolism/homeostasis 31 HP:0001939
13 cleft palate 31 HP:0000175
14 micrognathia 31 HP:0000347
15 epiphyseal stippling 31 HP:0010655
16 flat face 31 HP:0012368
17 alopecia 31 HP:0001596
18 cerebral cortical atrophy 31 HP:0002120
19 rhizomelia 31 HP:0008905
20 upslanted palpebral fissure 31 HP:0000582
21 severe short stature 31 HP:0003510
22 severe failure to thrive 31 HP:0001525
23 kyphoscoliosis 31 HP:0002751
24 coronal cleft vertebrae 31 HP:0003417
25 congenital cataract 31 HP:0000519
26 flared metaphysis 31 HP:0003015
27 delayed cns myelination 31 HP:0002188
28 calcific stippling of infantile cartilaginous skeleton 31 HP:0005841

UMLS symptoms related to Rhizomelic Chondrodysplasia Punctata, Type 1:


seizures, muscle spasticity

MGI Mouse Phenotypes related to Rhizomelic Chondrodysplasia Punctata, Type 1:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.25 ACOX1 DOK7 GNPAT HADHB HSD17B4 IL6R
2 homeostasis/metabolism MP:0005376 10.24 SCP2 UROD ACOX1 AGPS GNPAT HADHB
3 behavior/neurological MP:0005386 10.23 DOK7 HSD17B4 IL6R PEX2 PEX5 PEX5L
4 endocrine/exocrine gland MP:0005379 10.03 PEX2 PEX5 PEX7 ACOX1 AGPS GNPAT
5 immune system MP:0005387 10.02 ACOX1 HSD17B4 IL1A IL6R PEX5 PEX7
6 mortality/aging MP:0010768 9.97 PEX7 PHEX PLP1 RBFOX2 UROD AGPS
7 liver/biliary system MP:0005370 9.96 ACOX1 HADHB HSD17B4 IL6R PEX2 PEX5
8 nervous system MP:0003631 9.73 PEX5 PEX5L PEX7 PHEX PHYH PLP1
9 reproductive system MP:0005389 9.23 ACOX1 AGPS GNPAT HSD17B4 PEX5 PEX7

Drugs & Therapeutics for Rhizomelic Chondrodysplasia Punctata, Type 1

Search Clinical Trials , NIH Clinical Center for Rhizomelic Chondrodysplasia Punctata, Type 1

Genetic Tests for Rhizomelic Chondrodysplasia Punctata, Type 1

Genetic tests related to Rhizomelic Chondrodysplasia Punctata, Type 1:

# Genetic test Affiliating Genes
1 Rhizomelic Chondrodysplasia Punctata Type 1 28 PEX7

Anatomical Context for Rhizomelic Chondrodysplasia Punctata, Type 1

MalaCards organs/tissues related to Rhizomelic Chondrodysplasia Punctata, Type 1:

38
Bone, Eye

Publications for Rhizomelic Chondrodysplasia Punctata, Type 1

Articles related to Rhizomelic Chondrodysplasia Punctata, Type 1:

# Title Authors Year
1
Neonatal Rhizomelic Chondrodysplasia Punctata Type 1: Weaving Evidence Into Clinical Practice. ( 29068853 )
2017
2
Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene. ( 25800479 )
2015
3
Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1. ( 26587300 )
2015
4
Identification of a novel missense mutation of PEX7 gene in an Iranian patient with rhizomelic chondrodysplasia punctata type 1. ( 23357221 )
2013
5
Rhizomelic chondrodysplasia punctata type 1 and fulminant neonatal respiratory failure, a case report and discussion of pathophysiology. ( 22052861 )
2011
6
Second trimester prenatal diagnosis of rhizomelic chondrodysplasia punctata type 1 on ultrasound findings. ( 20014169 )
2010
7
Rhizomelic chondrodysplasia punctata type 1: report of mutations in 3 children from India. ( 20145307 )
2010
8
Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. ( 11781871 )
2002
9
Rhizomelic Chondrodysplasia Punctata Type 1 ( 20301447 )
1993

Variations for Rhizomelic Chondrodysplasia Punctata, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Rhizomelic Chondrodysplasia Punctata, Type 1:

71
# Symbol AA change Variation ID SNP ID
1 PEX7 p.Ala218Val VAR_007726 rs121909151

ClinVar genetic disease variations for Rhizomelic Chondrodysplasia Punctata, Type 1:

6 (show all 33)
# Gene Variation Type Significance SNP ID Assembly Location
1 PEX7 NM_000288.3(PEX7): c.854A> G (p.His285Arg) single nucleotide variant Pathogenic rs62653611 GRCh37 Chromosome 6, 137219330: 137219330
2 PEX7 NM_000288.3(PEX7): c.74C> T (p.Ser25Phe) single nucleotide variant Likely pathogenic rs61753236 GRCh37 Chromosome 6, 137143877: 137143877
3 PEX7 NM_000288.3(PEX7): c.188+1G> C single nucleotide variant Pathogenic rs267608254 GRCh37 Chromosome 6, 137146410: 137146410
4 PEX7 NM_000288.3(PEX7): c.400G> A (p.Asp134Asn) single nucleotide variant Likely pathogenic rs764346452 GRCh37 Chromosome 6, 137166813: 137166813
5 PEX7 NM_000288.3(PEX7): c.618G> A (p.Trp206Ter) single nucleotide variant Likely pathogenic rs61753245 GRCh37 Chromosome 6, 137187856: 137187856
6 PEX7 NM_000288.3(PEX7): c.875T> A (p.Leu292Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1805137 GRCh37 Chromosome 6, 137219351: 137219351
7 PEX7 NM_000288.3(PEX7): c.653C> T (p.Ala218Val) single nucleotide variant Pathogenic/Likely pathogenic rs121909151 GRCh37 Chromosome 6, 137191047: 137191047
8 PEX7 NM_000288.3(PEX7): c.649G> A (p.Gly217Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121909152 GRCh37 Chromosome 6, 137191043: 137191043
9 PEX7 NM_000288.3(PEX7): c.694C> T (p.Arg232Ter) single nucleotide variant Pathogenic/Likely pathogenic rs121909153 GRCh37 Chromosome 6, 137191088: 137191088
10 PEX7 NM_000288.3(PEX7): c.45_52dupGGGACGCC (p.His18Argfs) duplication Pathogenic rs199470486 GRCh37 Chromosome 6, 137143848: 137143855
11 PEX7 NM_000288.3(PEX7): c.903+1G> C single nucleotide variant Pathogenic rs148591292 GRCh37 Chromosome 6, 137219380: 137219380
12 PEX7 NM_000288.3(PEX7): c.345T> G (p.Tyr115Ter) single nucleotide variant Pathogenic/Likely pathogenic rs121909154 GRCh37 Chromosome 6, 137166758: 137166758
13 PEX7 NM_000288.3(PEX7): c.120C> G (p.Tyr40Ter) single nucleotide variant Pathogenic/Likely pathogenic rs61753238 GRCh37 Chromosome 6, 137143923: 137143923
14 PEX7 NM_000288.3(PEX7): c.40A> C (p.Thr14Pro) single nucleotide variant Pathogenic rs61753233 GRCh37 Chromosome 6, 137143843: 137143843
15 PEX7 NM_000288.3(PEX7): c.183delT (p.Phe61Leufs) deletion Likely pathogenic rs1085307085 GRCh38 Chromosome 6, 136825266: 136825266
16 PEX7 NM_000288.3(PEX7): c.13_19dupTGCGGTG (p.Gly7Valfs) duplication Pathogenic/Likely pathogenic rs62636519 GRCh38 Chromosome 6, 136822678: 136822684
17 PEX7 NM_000288.3(PEX7): c.31_56del26 (p.Met11Leufs) deletion Likely pathogenic rs1057516961 GRCh37 Chromosome 6, 137143834: 137143859
18 PEX7 NM_000288.3(PEX7): c.60C> G (p.Tyr20Ter) single nucleotide variant Likely pathogenic rs1057516882 GRCh37 Chromosome 6, 137143863: 137143863
19 PEX7 NM_000288.3(PEX7): c.81C> G (p.Tyr27Ter) single nucleotide variant Likely pathogenic rs1057516737 GRCh37 Chromosome 6, 137143884: 137143884
20 PEX7 NM_000288.3(PEX7): c.130+1G> C single nucleotide variant Likely pathogenic rs267608253 GRCh37 Chromosome 6, 137143934: 137143934
21 PEX7 NM_000288.3(PEX7): c.277C> T (p.Gln93Ter) single nucleotide variant Likely pathogenic rs763514968 GRCh37 Chromosome 6, 137147545: 137147545
22 PEX7 NM_000288.3(PEX7): c.334C> T (p.Gln112Ter) single nucleotide variant Likely pathogenic rs62653604 GRCh37 Chromosome 6, 137147602: 137147602
23 PEX7 NM_000288.3(PEX7): c.339+2T> C single nucleotide variant Likely pathogenic rs1057517059 GRCh38 Chromosome 6, 136826471: 136826471
24 PEX7 NM_000288.3(PEX7): c.508delT (p.Cys170Valfs) deletion Likely pathogenic rs1057516827 GRCh37 Chromosome 6, 137167301: 137167301
25 PEX7 NM_000288.3(PEX7): c.527-2A> G single nucleotide variant Likely pathogenic rs1057517339 GRCh38 Chromosome 6, 136866625: 136866625
26 PEX7 NM_000288.3(PEX7): c.545dupT (p.Trp183Metfs) duplication Likely pathogenic rs1057516574 GRCh38 Chromosome 6, 136866645: 136866645
27 PEX7 NM_000288.3(PEX7): c.633+1G> A single nucleotide variant Likely pathogenic rs1057516989 GRCh38 Chromosome 6, 136866734: 136866734
28 PEX7 NM_000288.3(PEX7): c.736_747+17del29 deletion Likely pathogenic rs1057517257 GRCh37 Chromosome 6, 137191130: 137191158
29 PEX7 NM_000288.3(PEX7): c.748-2A> G single nucleotide variant Likely pathogenic rs778862698 GRCh38 Chromosome 6, 136872196: 136872196
30 PEX7 NM_000288.3(PEX7): c.774_784delGGCCTCTTGCT (p.Ala259Valfs) deletion Likely pathogenic rs1057516824 GRCh37 Chromosome 6, 137193362: 137193372
31 PEX7 NM_000288.3(PEX7): c.357G> A (p.Trp119Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 6, 136845632: 136845632
32 PEX7 NM_000288.3(PEX7): c.538delC (p.Leu180Terfs) deletion Pathogenic GRCh37 Chromosome 6, 137187776: 137187776
33 PEX7 NM_000288.3(PEX7): c.641T> C (p.Leu214Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 136869897: 136869897

Expression for Rhizomelic Chondrodysplasia Punctata, Type 1

Search GEO for disease gene expression data for Rhizomelic Chondrodysplasia Punctata, Type 1.

Pathways for Rhizomelic Chondrodysplasia Punctata, Type 1

GO Terms for Rhizomelic Chondrodysplasia Punctata, Type 1

Cellular components related to Rhizomelic Chondrodysplasia Punctata, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.97 ACOX1 AGPS DOK7 GNPAT HADHB HSD17B4
2 peroxisome GO:0005777 9.9 ACOX1 AGPS FAR1 GNPAT HSD17B4 PEX12
3 peroxisomal membrane GO:0005778 9.61 ACOX1 AGPS FAR1 GNPAT HSD17B4 PEX12
4 integral component of peroxisomal membrane GO:0005779 9.43 FAR1 PEX12 PEX2
5 peroxisomal matrix GO:0005782 9.23 ACOX1 AGPS FAR1 GNPAT HSD17B4 PEX7
6 membrane GO:0016020 10.24 ACOX1 AGPS DOK7 FAR1 GNPAT HADHB

Biological processes related to Rhizomelic Chondrodysplasia Punctata, Type 1 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.93 ACOX1 AGPS FAR1 HSD17B4 PHYH
2 lipid metabolic process GO:0006629 9.89 ACOX1 AGPS FAR1 HADHB HSD17B4
3 fatty acid metabolic process GO:0006631 9.76 ACOX1 HADHB HSD17B4 PHYH
4 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.58 ACOX1 HSD17B4 SCP2
5 protein import into peroxisome matrix GO:0016558 9.56 PEX12 PEX2 PEX5 PEX7
6 peroxisome organization GO:0007031 9.55 PEX12 PEX2 PEX5 PEX7 SCP2
7 alpha-linolenic acid metabolic process GO:0036109 9.54 ACOX1 HSD17B4 SCP2
8 bile acid biosynthetic process GO:0006699 9.52 HSD17B4 SCP2
9 cellular lipid metabolic process GO:0044255 9.51 GNPAT PEX5
10 very long-chain fatty acid metabolic process GO:0000038 9.5 ACOX1 HSD17B4 PEX2
11 protein targeting to peroxisome GO:0006625 9.48 PEX12 PEX7
12 protein import into peroxisome matrix, docking GO:0016560 9.43 PEX5 PEX5L
13 ether lipid biosynthetic process GO:0008611 9.26 AGPS FAR1 GNPAT PEX7
14 fatty acid beta-oxidation GO:0006635 9.1 ACOX1 HADHB HSD17B4 PEX2 PEX5 PEX7

Molecular functions related to Rhizomelic Chondrodysplasia Punctata, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.72 ACOX1 AGPS FAR1 HSD17B4 PHYH
2 small GTPase binding GO:0031267 9.4 PEX5 PEX5L
3 FAD binding GO:0071949 9.37 ACOX1 AGPS
4 transferase activity, transferring acyl groups other than amino-acyl groups GO:0016747 9.26 HADHB SCP2
5 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.16 HADHB HSD17B4
6 peroxisome targeting sequence binding GO:0000268 8.96 PEX5 PEX5L
7 peroxisome matrix targeting signal-1 binding GO:0005052 8.62 PEX5 PEX5L

Sources for Rhizomelic Chondrodysplasia Punctata, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....