LH3 DEFICIENCY
MCID: BNF003
MIFTS: 25

Bone Fragility with Contractures, Arterial Rupture, and Deafness (LH3 DEFICIENCY)

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

Aliases & Classifications for Bone Fragility with Contractures, Arterial Rupture, and Deafness

MalaCards integrated aliases for Bone Fragility with Contractures, Arterial Rupture, and Deafness:

Name: Bone Fragility with Contractures, Arterial Rupture, and Deafness 57 29 6 39 71
Lysyl Hydroxylase 3 Deficiency 57 73 36 13
Lh3 Deficiency 57 73
Bone Fragility-Contractures-Arterial Rupture-Hearing Loss Syndrome 58
Connective Tissue Disorder Due to Lysyl Hydroxylase-3 Deficiency 58
Bone Fragility-Contractures-Arterial Rupture-Deafness Syndrome 58
Bone Fragility with Contractures Arterial Rupture and Deafness 73
Connective Tissue Disorder Due to Lh3 Deficiency 58

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive


HPO:

31
bone fragility with contractures, arterial rupture, and deafness:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Rare systemic and rhumatological diseases
Developmental anomalies during embryogenesis


Summaries for Bone Fragility with Contractures, Arterial Rupture, and Deafness

KEGG : 36 Lysyl hydroxylase 3 (LH3) deficiency is a connective tissue disorder, caused by defects in PLOD3 that encodes LH3. This disease is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders. In addition to lysyl hydroxylase activity, LH3 has also collagen galactosyltransferase and glucosyltransferase activities. It has been reported that one mutation dramatically reduced the sugar-transfer activity of LH3.

MalaCards based summary : Bone Fragility with Contractures, Arterial Rupture, and Deafness, is also known as lysyl hydroxylase 3 deficiency. An important gene associated with Bone Fragility with Contractures, Arterial Rupture, and Deafness is PLOD3 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3), and among its related pathways/superpathways are Lysine degradation and Other types of O-glycan biosynthesis. Affiliated tissues include bone, and related phenotypes are scoliosis and osteopenia

UniProtKB/Swiss-Prot : 73 Lysyl hydroxylase 3 deficiency: Connective tissue disorder. The syndrome is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders, most of them involving COL2A1 (type II collagen). The findings suggest that the failure of lysyl hydroxylation and hydroxylysyl carbohydrate addition, which affects many collagens, is the molecular basis of this syndrome.

More information from OMIM: 612394

Related Diseases for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Symptoms & Phenotypes for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Human phenotypes related to Bone Fragility with Contractures, Arterial Rupture, and Deafness:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 HP:0002650
2 osteopenia 31 HP:0000938
3 hearing impairment 31 HP:0000365
4 cataract 31 HP:0000518
5 global developmental delay 31 HP:0001263
6 short nose 31 HP:0003196
7 anteverted nares 31 HP:0000463
8 coarse hair 31 HP:0002208
9 flat face 31 HP:0012368
10 intrauterine growth retardation 31 HP:0001511
11 postnatal growth retardation 31 HP:0008897
12 low-set ears 31 HP:0000369
13 myopia 31 HP:0000545
14 elbow flexion contracture 31 HP:0002987
15 talipes equinovarus 31 HP:0001762
16 downturned corners of mouth 31 HP:0002714
17 long philtrum 31 HP:0000343
18 platyspondyly 31 HP:0000926
19 malar flattening 31 HP:0000272
20 bruising susceptibility 31 HP:0000978
21 nail dysplasia 31 HP:0002164
22 abnormality of the pinna 31 HP:0000377
23 j-shaped sella turcica 31 HP:0002680
24 arterial rupture 31 HP:0025019
25 pathologic fracture 31 HP:0002756
26 hypoplasia of the capital femoral epiphysis 31 HP:0003090
27 thenar muscle atrophy 31 HP:0003393
28 dilatation of the cerebral artery 31 HP:0004944
29 shallow orbits 31 HP:0000586
30 decreased palmar creases 31 HP:0006184
31 diaphragmatic eventration 31 HP:0009110

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skeletal:
osteopenia
pathologic fractures

Skin Nails Hair Hair:
coarse hair

Head And Neck Ears:
low-set ears
simple ears
hearing loss, bilateral sensorineural (profound)

Skeletal Feet:
talipes equinovarus

Head And Neck Face:
long philtrum
flat facial profile

Skeletal Skull:
j-shaped sella turcica

Skeletal Hands:
thenar muscle atrophy
decreased palmar creases
hypothenar muscle atrophy
flexion contractures (pip joints)

Chest Diaphragm:
diaphragmatic eventration

Skin Nails Hair Nails:
dysplastic nails

Skeletal Limbs:
elbow contractures
prominent knees

Muscle Soft Tissue:
reduced muscle mass

Growth Weight:
birth weight below 0.3 percentile

Head And Neck Nose:
short nose
anteverted nares

Growth Other:
postnatal growth retardation
intrauterine growth retardation (iugr)

Head And Neck Eyes:
myopia
shallow orbits
cataracts

Head And Neck Mouth:
downturned corners of mouth

Skeletal Spine:
platyspondyly
scoliosis (progressive)
small odontoid

Cardiovascular Vascular:
arterial rupture
popliteal aneurysm
cerebral aneurysm

Skin Nails Hair Skin:
decreased palmar creases
easy bruisability
blistering (fingers, toes, pinnae)

Neurologic Central Nervous System:
developmental delay
cerebral arterial hemorrhage

Head And Neck Teeth:
normal teeth

Skeletal Pelvis:
small capital femoral epiphyses

Growth Height:
birth length below 0.3 percentile

Laboratory Abnormalities:
abnormal urinary collagen-derived pyridinium crosslinks (absent glc-gal-pyd)
decreased serum glucosyltransferase (ggt) activity

Clinical features from OMIM®:

612394 (Updated 05-Mar-2021)

Drugs & Therapeutics for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Search Clinical Trials , NIH Clinical Center for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Genetic Tests for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Genetic tests related to Bone Fragility with Contractures, Arterial Rupture, and Deafness:

# Genetic test Affiliating Genes
1 Bone Fragility with Contractures, Arterial Rupture, and Deafness 29 PLOD3

Anatomical Context for Bone Fragility with Contractures, Arterial Rupture, and Deafness

MalaCards organs/tissues related to Bone Fragility with Contractures, Arterial Rupture, and Deafness:

40
Bone

Publications for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Articles related to Bone Fragility with Contractures, Arterial Rupture, and Deafness:

# Title Authors PMID Year
1
A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene. 57 6
18834968 2008

Variations for Bone Fragility with Contractures, Arterial Rupture, and Deafness

ClinVar genetic disease variations for Bone Fragility with Contractures, Arterial Rupture, and Deafness:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLOD3 NM_001084.5(PLOD3):c.668A>G (p.Asn223Ser) SNV Pathogenic 6643 rs121434414 7:100858381-100858381 7:101215100-101215100
2 PLOD3 NM_001084.5(PLOD3):c.2071del (p.Cys691fs) Deletion Pathogenic 6644 rs786205872 7:100849708-100849708 7:101206427-101206427
3 PLOD3 NM_001084.5(PLOD3):c.1890T>G (p.Tyr630Ter) SNV Likely pathogenic 225442 rs748105435 7:100850904-100850904 7:101207623-101207623
4 PLOD3 NM_001084.5(PLOD3):c.809C>T (p.Pro270Leu) SNV Likely pathogenic 623469 rs1562894320 7:100856193-100856193 7:101212912-101212912
5 PLOD3 NM_001084.5(PLOD3):c.1684C>T (p.Pro562Ser) SNV Uncertain significance 915354 7:100852238-100852238 7:101208957-101208957
6 PLOD3 NM_001084.5(PLOD3):c.887C>G (p.Pro296Arg) SNV Uncertain significance 547022 rs143577626 7:100855929-100855929 7:101212648-101212648
7 PLOD3 NM_001084.5(PLOD3):c.1678G>C (p.Glu560Gln) SNV Likely benign 624295 rs140879834 7:100853379-100853379 7:101210098-101210098
8 PLOD3 NM_001084.5(PLOD3):c.1935+105T>G SNV Likely benign 440181 rs186082235 7:100850754-100850754 7:101207473-101207473
9 PLOD3 NM_001084.5(PLOD3):c.1179C>T (p.Ala393=) SNV Benign 440177 rs11546152 7:100855180-100855180 7:101211899-101211899
10 PLOD3 NM_001084.5(PLOD3):c.1402C>G (p.Arg468Gly) SNV Benign 618835 rs75592752 7:100853911-100853911 7:101210630-101210630
11 PLOD3 NM_001084.5(PLOD3):c.1797G>A (p.Arg599=) SNV Benign 771160 rs139049819 7:100850997-100850997 7:101207716-101207716
12 PLOD3 NM_001084.5(PLOD3):c.1977C>T (p.Asp659=) SNV Benign 440171 rs11546151 7:100850144-100850144 7:101206863-101206863
13 PLOD3 NM_001084.5(PLOD3):c.570C>T (p.Asp190=) SNV Benign 440175 rs35159414 7:100859234-100859234 7:101215953-101215953
14 PLOD3 NM_001084.5(PLOD3):c.1233-4G>A SNV Benign 440176 rs2301903 7:100855001-100855001 7:101211720-101211720
15 PLOD3 NM_001084.5(PLOD3):c.1144G>C (p.Asp382His) SNV Benign 440182 rs41281013 7:100855215-100855215 7:101211934-101211934
16 PLOD3 NM_001084.5(PLOD3):c.1986G>A (p.Pro662=) SNV Benign 717332 rs117761436 7:100850135-100850135 7:101206854-101206854

UniProtKB/Swiss-Prot genetic disease variations for Bone Fragility with Contractures, Arterial Rupture, and Deafness:

73
# Symbol AA change Variation ID SNP ID
1 PLOD3 p.Asn223Ser VAR_054913 rs121434414

Expression for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Search GEO for disease gene expression data for Bone Fragility with Contractures, Arterial Rupture, and Deafness.

Pathways for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Pathways related to Bone Fragility with Contractures, Arterial Rupture, and Deafness according to KEGG:

36
# Name Kegg Source Accession
1 Lysine degradation hsa00310
2 Other types of O-glycan biosynthesis hsa00514

GO Terms for Bone Fragility with Contractures, Arterial Rupture, and Deafness

Sources for Bone Fragility with Contractures, Arterial Rupture, and Deafness

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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