BCYM4
MCID: BRC120
MIFTS: 36

Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes (BCYM4)

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

Aliases & Classifications for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

MalaCards integrated aliases for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

Name: Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes 56 73
Spondyloepimetaphyseal Dysplasia, Pakistani Type 56 12 58 29 6 15 71
Brachyolmia 4 with Mild Epiphyseal and Metaphyseal Changes 56 13
Spondylodysplasia and Premature Pubarche 56 73
Semd, Pakistani Type 56 36
Bcym4 56 73
Brachyolmia, Type 4, with Mild Epiphyseal and Metaphyseal Changes 39
Spondyloepimetaphyseal Dysplasia Pakistani Type 12
Spondylometaepiphyseal Dysplasia Pakistani Type 73
Spondyloepimetaphyseal Dysplasia, Papss2 Type 58
Semd Pakistani Type 73

Characteristics:

Orphanet epidemiological data:

58
spondyloepimetaphyseal dysplasia, papss2 type
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
skeletal and endocrine features have not been fully characterized in all of the patients reported


HPO:

31
brachyolmia type 4 with mild epiphyseal and metaphyseal changes:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050812
OMIM 56 612847
KEGG 36 H00761
MeSH 43 D001848
ICD10 via Orphanet 33 Q77.7
UMLS via Orphanet 72 C2748515
Orphanet 58 ORPHA93282
UMLS 71 C2748515

Summaries for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

UniProtKB/Swiss-Prot : 73 Brachyolmia type 4 with mild epiphyseal and metaphyseal changes: A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM4 is an autosomal recessive form with mild epiphyseal and metaphyseal changes. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some BCYM4 patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.

MalaCards based summary : Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes, also known as spondyloepimetaphyseal dysplasia, pakistani type, is related to spondyloepimetaphyseal dysplasia, matrilin-3 related and brachyolmia type 1, hobaek type. An important gene associated with Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes is PAPSS2 (3'-Phosphoadenosine 5'-Phosphosulfate Synthase 2), and among its related pathways/superpathways are Purine metabolism and Selenocompound metabolism. Affiliated tissues include bone, and related phenotypes are short stature and acne

Disease Ontology : 12 A spondyloepimetaphyseal dysplasia that is characterized by short stature, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, and normal intelligence.

OMIM : 56 This form of brachyolmia, here designated brachyolmia type 4, is characterized by short-trunk stature with normal intelligence and facies. The radiographic features include rectangular vertebral bodies with irregular endplates and narrow intervertebral discs, precocious calcification of rib cartilages, short femoral neck, mildly shortened metacarpals, and mild epiphyseal and metaphyseal changes of the tubular bones (summary by Miyake et al., 2012). (612847)

KEGG : 36 Spondyloepimetaphyseal dysplasia (SEMD) Pakistani type, also known as brachyolmia type 4, is characterized by short, bowed lower limbs, mild brachydactyly, enlarged knee joints, and early-onset osteoarthropathy. Radiographs show delayed epiphyseal ossification in hips and knees. Nonsense mutation in ATPSK2/PAPSS2 has been reported.

Related Diseases for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Diseases related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 spondyloepimetaphyseal dysplasia, matrilin-3 related 29.8 SEMA3A PAPSS2
2 brachyolmia type 1, hobaek type 11.3
3 coxa vara 10.2
4 hyperandrogenism 10.2
5 hyperuricemic nephropathy, familial juvenile, 1 10.0 SHROOM3 MUC1
6 dysgerminoma 9.8 MUC1 FGFR2
7 brachyolmia 9.8 SEMA3A PAPSS2
8 radioulnar synostosis 9.8 MECOM FGFR2
9 endometrial adenocarcinoma 9.7 MUC1 FGFR2
10 calcinosis 9.5 MUC1 FGFR2
11 odontochondrodysplasia 9.4 SEMA3A PAPSS2 FGFR2
12 neuroma 9.4 SEMA3A MUC1

Graphical network of the top 20 diseases related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:



Diseases related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Symptoms & Phenotypes for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Human phenotypes related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 short stature 31 HP:0004322
2 acne 31 HP:0001061
3 secondary amenorrhea 31 HP:0000869
4 kyphoscoliosis 31 HP:0002751
5 brachydactyly 31 HP:0001156
6 platyspondyly 31 HP:0000926
7 hirsutism 31 HP:0001007
8 irregular vertebral endplates 31 HP:0003301
9 lower limb undergrowth 31 HP:0009816
10 spondyloepimetaphyseal dysplasia 31 HP:0002651
11 bowing of the legs 31 HP:0002979
12 premature pubarche 31 HP:0012411
13 lumbar scoliosis 31 HP:0004626

Symptoms via clinical synopsis from OMIM:

56
Growth Height:
short stature

Endocrine Features:
secondary amenorrhea
hyperandrogenism
premature pubarche (in 1 female patient)

Skin Nails Hair Hair:
hirsutism

Skeletal Limbs:
short and bowed lower limbs
enlarged knee joints
metaphyseal changes, mild, of knees and hips
osteoarthropathy, precocious

Skin Nails Hair Skin:
acne

Skeletal Spine:
kyphoscoliosis
platyspondyly
lumbar scoliosis
irregular end plates

Skeletal Hands:
brachydactyly, mild

Laboratory Abnormalities:
elevated androstenedione and testosterone
dehydroepiandrosterone (dhea) at upper level of normal range
dhea sulfotransferase below limit of detection

Clinical features from OMIM:

612847

GenomeRNAi Phenotypes related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-113 9.53 ATP2B1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-126 9.53 TRPM6
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.53 TRPM6
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-141 9.53 ATP2B1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-151 9.53 PAPSS2
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.53 PAPSS2 TRPM6
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.53 TRPM6
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-183 9.53 ATP2B1 PAPSS2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.53 ATP2B1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.53 ATP2B1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-63 9.53 ATP2B1
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.53 ATP2B1
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-73 9.53 TRPM6
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-81 9.53 PAPSS2

MGI Mouse Phenotypes related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.65 FGFR2 MECOM PAPSS2 SHROOM3 TRPM6
2 embryo MP:0005380 9.55 ATP2B1 FGFR2 MECOM SHROOM3 TRPM6
3 growth/size/body region MP:0005378 9.5 ATP2B1 FGFR2 MECOM PAPSS2 SEMA3A SHROOM3
4 skeleton MP:0005390 9.17 ATP2B1 FGFR2 MECOM PAPSS2 SEMA3A SHROOM3

Drugs & Therapeutics for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Search Clinical Trials , NIH Clinical Center for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Genetic Tests for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Genetic tests related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

# Genetic test Affiliating Genes
1 Spondyloepimetaphyseal Dysplasia, Pakistani Type 29 PAPSS2

Anatomical Context for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

MalaCards organs/tissues related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

40
Bone

Publications for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Articles related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

# Title Authors PMID Year
1
PAPSS2 mutations cause autosomal recessive brachyolmia. 56 6
22791835 2012
2
Inactivating PAPSS2 mutations in a patient with premature pubarche. 56 6
19474428 2009
3
Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse. 6 56
9771708 1998
4
Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred. 56 6
9714015 1998
5
Spondyloepimetaphyseal dysplasia Pakistani type: expansion of the phenotype. 61
23633440 2013

Variations for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

ClinVar genetic disease variations for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

6 (show all 26) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PAPSS2 NM_001015880.2(PAPSS2):c.683_684del (p.Phe228fs)deletion Pathogenic 572534 rs1471554906 10:89474784-89474785 10:87715027-87715028
2 PAPSS2 NM_001015880.2(PAPSS2):c.1439C>A (p.Ser480Ter)SNV Pathogenic 6686 rs121908950 10:89503346-89503346 10:87743589-87743589
3 PAPSS2 NM_001015880.2(PAPSS2):c.143C>G (p.Thr48Arg)SNV Pathogenic 6687 rs121908951 10:89469068-89469068 10:87709311-87709311
4 PAPSS2 NM_001015880.2(PAPSS2):c.1000C>T (p.Arg334Ter)SNV Pathogenic 6688 rs121908952 10:89487160-89487160 10:87727403-87727403
5 PAPSS2 NM_001015880.2(PAPSS2):c.337dup (p.Ala113fs)duplication Pathogenic 39642 rs606231241 10:89473022-89473023 10:87713265-87713266
6 PAPSS2 NM_001015880.2(PAPSS2):c.616_634del (p.Val206fs)deletion Pathogenic 39643 rs606231242 10:89474595-89474613 10:87714838-87714856
7 PAPSS2 NM_001015880.2(PAPSS2):c.1305_1306AG[2] (p.Arg437fs)short repeat Pathogenic 39644 rs786200933 10:89503212-89503213 10:87743455-87743456
8 PAPSS2 NM_001015880.2(PAPSS2):c.477_480dup (p.Lys161fs)duplication Pathogenic 39645 rs606231243 10:89473894-89473895 10:87714137-87714138
9 PAPSS2 NM_001015880.2(PAPSS2):c.661del (p.Ile221fs)deletion Pathogenic 39646 rs786200934 10:89474762-89474762 10:87715005-87715005
10 PAPSS2 NM_001015880.2(PAPSS2):c.1657_1661ATTCC[1] (p.Phe555fs)short repeat Likely pathogenic 208601 rs797045099 10:89504923-89504927 10:87745166-87745170
11 PAPSS2 NM_001015880.2(PAPSS2):c.809G>A (p.Gly270Asp)SNV Conflicting interpretations of pathogenicity 287596 rs138943074 10:89475544-89475544 10:87715787-87715787
12 PAPSS2 NM_001015880.2(PAPSS2):c.1648G>C (p.Val550Leu)SNV Uncertain significance 863873 10:89504915-89504915 10:87745158-87745158
13 PAPSS2 NM_001015880.2(PAPSS2):c.547G>A (p.Glu183Lys)SNV Uncertain significance 578450 rs774709274 10:89474528-89474528 10:87714771-87714771
14 PAPSS2 NM_001015880.2(PAPSS2):c.1849_1851del (p.Glu617del)deletion Uncertain significance 582845 rs563421338 10:89505715-89505717 10:87745958-87745960
15 PAPSS2 NM_001015880.2(PAPSS2):c.1683C>G (p.Asn561Lys)SNV Uncertain significance 661369 10:89504950-89504950 10:87745193-87745193
16 PAPSS2 NM_001015880.2(PAPSS2):c.1687G>A (p.Ala563Thr)SNV Uncertain significance 655993 10:89504954-89504954 10:87745197-87745197
17 PAPSS2 NM_001015880.2(PAPSS2):c.1350C>T (p.Gly450=)SNV Likely benign 770766 10:89503257-89503257 10:87743500-87743500
18 PAPSS2 NM_001015880.2(PAPSS2):c.375C>T (p.Phe125=)SNV Benign/Likely benign 283365 rs145230931 10:89473061-89473061 10:87713304-87713304
19 PAPSS2 NM_001015880.2(PAPSS2):c.886G>A (p.Val296Met)SNV Benign 500278 rs45467596 10:89487046-89487046 10:87727289-87727289
20 PAPSS2 NM_001015880.2(PAPSS2):c.1403C>T (p.Ala468Val)SNV Benign 537719 rs34097979 10:89503310-89503310 10:87743553-87743553
21 PAPSS2 NM_001015880.2(PAPSS2):c.276T>C (p.Ser92=)SNV Benign 537718 rs17124941 10:89472962-89472962 10:87713205-87713205
22 PAPSS2 NM_001015880.2(PAPSS2):c.267C>T (p.Leu89=)SNV Benign 779934 10:89472953-89472953 10:87713196-87713196
23 PAPSS2 NM_001015880.2(PAPSS2):c.477C>T (p.Asp159=)SNV Benign 782953 10:89473896-89473896 10:87714139-87714139
24 PAPSS2 NM_001015880.2(PAPSS2):c.753+4A>CSNV Benign 787187 10:89474859-89474859 10:87715102-87715102
25 PAPSS2 NM_001015880.2(PAPSS2):c.841A>T (p.Met281Leu)SNV Benign 776523 10:89475576-89475576 10:87715819-87715819
26 PAPSS2 NM_001015880.2(PAPSS2):c.861A>G (p.Leu287=)SNV Benign 282996 rs150727538 10:89475596-89475596 10:87715839-87715839

UniProtKB/Swiss-Prot genetic disease variations for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes:

73
# Symbol AA change Variation ID SNP ID
1 PAPSS2 p.Thr48Arg VAR_063049 rs121908951
2 PAPSS2 p.Cys43Tyr VAR_073026
3 PAPSS2 p.Leu76Gln VAR_073027
4 PAPSS2 p.Gly270Asp VAR_073029 rs138943074

Expression for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Search GEO for disease gene expression data for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes.

Pathways for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Pathways related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Selenocompound metabolism hsa00450
3 Sulfur metabolism hsa00920
4 Metabolic pathways hsa01100

Pathways related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.39 TRPM6 ATP2B1

GO Terms for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

Cellular components related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 8.92 TRPM6 SHROOM3 MUC1 ATP2B1

Biological processes related to Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 bone development GO:0060348 8.62 PAPSS2 FGFR2

Sources for Brachyolmia Type 4 with Mild Epiphyseal and Metaphyseal Changes

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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