Desbuquois dysplasia

Summary

Desbuquois dysplasia (MONDO:0015426) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000501	Glaucoma	Very frequent (80-99%)
HP:0000520	Proptosis	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001591	Bell-shaped thorax	Very frequent (80-99%)
HP:0002999	Patellar dislocation	Very frequent (80-99%)
HP:0003366	Abnormality of the femoral neck or head region	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0005616	Accelerated skeletal maturation	Very frequent (80-99%)
HP:0008873	Disproportionate short-limb short stature	Very frequent (80-99%)
HP:0010318	Aplasia/Hypoplasia of the abdominal wall musculature	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0000499	Abnormal eyelash morphology	Frequent (30-79%)
HP:0000592	Blue sclerae	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002673	Coxa valga	Frequent (30-79%)
HP:0002812	Coxa vara	Frequent (30-79%)
HP:0002816	Genu recurvatum	Frequent (30-79%)
HP:0002974	Radioulnar synostosis	Frequent (30-79%)
HP:0003042	Elbow dislocation	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0008070	Sparse hair	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Desbuquois dysplasia
Mondo ID	MONDO:0015426
OMIM	251450
Orphanet	1425
DOID	DOID:0060462
NCIT	C124056
SNOMED CT	254099008
UMLS	C0432242
MedGen	98479
GARD	0001818
Is cancer (heuristic)	no

Also known as: DBQD · Desbuquois dysplasia · desbuquois syndrome · micromelic dwarfism, narrow chest, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification

Data availability: 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › Desbuquois dysplasia

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

Subtypes (2): Desbuquois dysplasia 1, Desbuquois dysplasia 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CANT1	Definitive	Autosomal recessive	Desbuquois dysplasia 1	4
XYLT1	Strong	Autosomal recessive	Desbuquois dysplasia 2	5
FAM20B	Moderate	Autosomal recessive	Desbuquois dysplasia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG
CANT1	Orphanet:1425	Desbuquois syndrome
CANT1	Orphanet:647676	Multiple epiphyseal dysplasia type 7

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	gencc
CANT1	HGNC:19721	ENSG00000171302	Q8WVQ1	Soluble calcium-activated nucleotidase 1	gencc
FAM20B	HGNC:23017	ENSG00000116199	O75063	Glycosaminoglycan xylosylkinase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
CANT1	Soluble calcium-activated nucleotidase 1	Calcium-dependent nucleotidase with a preference for UDP.
FAM20B	Glycosaminoglycan xylosylkinase	Responsible for the 2-O-phosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature GAG chains.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
CANT1	Enzyme (other)	yes	3.6.1.5	Apyrase, Apyrase_sf
FAM20B	Other/Unknown	no		FAM20_C, FAM20

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
hair follicle	1
tibia	1
colonic mucosa	1
mucosa of transverse colon	1
pancreatic ductal cell	1
Brodmann (1909) area 10	1
lateral nuclear group of thalamus	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle
CANT1	280	ubiquitous	marker	pancreatic ductal cell, mucosa of transverse colon, colonic mucosa
FAM20B	294	ubiquitous	marker	lateral nuclear group of thalamus, Brodmann (1909) area 10, saphenous vein

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CANT1	1,231
FAM20B	960
XYLT1	704

Intra-cohort edges

A	B	Sources
CANT1	FAM20B	string_interaction
CANT1	XYLT1	string_interaction
FAM20B	XYLT1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XYLT1	Q86Y38	9
CANT1	Q8WVQ1	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM20B	O75063	93.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycosaminoglycan-protein linkage region biosynthesis	2	262.5×	7e-05	XYLT1, FAM20B
Innate Immune System	1	8.5×	0.166	CANT1
Neutrophil degranulation	1	7.7×	0.166	CANT1
Immune System	1	4.3×	0.214	CANT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
proteoglycan biosynthetic process	3	842.6×	1e-08	XYLT1, CANT1, FAM20B
negative regulation of proteoglycan biosynthetic process	1	2808.7×	0.002	FAM20B
glycosaminoglycan-protein linkage region biosynthetic process	1	1404.3×	0.002	XYLT1
ossification involved in bone maturation	1	468.1×	0.005	XYLT1
glycosaminoglycan biosynthetic process	1	280.9×	0.006	XYLT1
chondroitin sulfate proteoglycan biosynthetic process	1	208.1×	0.007	XYLT1
heparan sulfate proteoglycan biosynthetic process	1	187.2×	0.007	XYLT1
embryonic skeletal system development	1	130.6×	0.009	XYLT1
positive regulation of canonical NF-kappaB signal transduction	1	24.2×	0.041	CANT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
XYLT1	0	0
CANT1	0	0
FAM20B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
XYLT1	2.4.2.26	protein xylosyltransferase
CANT1	3.6.1.5	apyrase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	XYLT1, CANT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FAM20B

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
XYLT1	0	—
CANT1	0	—
FAM20B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.