Skeletal dysplasia
Gene: LTBP3
Dental anomalies with short stature is recessive. Several cases reported - pathogenic variant almost missed because gene was tiered under AD mode of inheritance only.Created: 14 Feb 2022, 10:35 p.m. | Last Modified: 14 Feb 2022, 10:35 p.m.
Panel Version: 2.170
spondylo-epi-(meta)-physeal dysplasias gp of SD. At least 3 cases reported.; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Geleophysic dysplasia 3 617809; Dental anomalies and short stature 610216
Publications
Variants in this GENE are reported as part of current diagnostic practice
The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 2:18 p.m. | Last Modified: 30 Jan 2023, 2:28 p.m.
Panel Version: 3.5
Comment on mode of inheritance: The mode of inheritance should be updated to Both mono- and bi-allelic at the next GMS review.Created: 2 Mar 2022, 5:40 p.m. | Last Modified: 2 Mar 2022, 5:40 p.m.
Panel Version: 2.172
This gene originally had the mode of inheritance set to monoallelic based on the Geleophysic dysplasia 3 OMIM:617809 phenotype. This is supported by heterozygous variants in LTBP3 reported in PMID: 27068007 (McInerney-Leo et al 2016) - 2 cases with geleophysic dysplasia and 1 with acromelic dysplasia and PMID: 33082559 (Marzin et al 2021) - 2 cases with geleophysic dysplasia and 1 with acromelic dysplasia . Dental anomalies are not reported in either set of cases.
As Tracy Lester reports there are more than 3 cases of patients with both a dental phenotype and short stature and so the mode of inheritance should be updated to both mono- and bi-allelic.
PMID: 25899461 - Dugan et al 2015 - 2 sisters with homozygous truncating mutations (1 bp insertion) in LTBP3. Only this gene was analysed. They presented with oligodontia, short stature and mitral valve prolapse.
PMID: 25669657 - Huckert et al 2015 - report 4 families (3 consanguineous) with a phenotype of significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta. WES identified homozygous or compound het protein altering variants in LTBP3 in all patients (14 bp deletion, nonsense variant, splice site variant, 2 1bp deletions).
PMID:19344874 - Noor et al 2009 - consanguineous Pakistani family with oligodontia along with short stature in an autosomal-recessive fashion. A homozygous nonsense mutation, Y774X, within LTBP3 was identified.
PMID: 8721563 (abstract only accessed) and PMID: 19213025 report patients with a dental and skeletal phenotype but no genetic analysis.Created: 2 Mar 2022, 5 p.m. | Last Modified: 2 Mar 2022, 5:39 p.m.
Panel Version: 2.171
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: LTBP3; Initial rating suggestion: greenCreated: 6 Mar 2019, 11:36 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on phenotypes: Dental anomalies and short stature 601216 associated with biallelic LTBP3 variantsCreated: 6 Feb 2018, 10:40 a.m.
Associated with Geleophysic dysplasia 3 617809 phenotype in OMIM, not in G2P. At least 3 variants reported in 3 unrelated casesCreated: 6 Feb 2018, 10:39 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Geleophysic dysplasia 3 617809
Publications
Tag Q1_22_NHS_review was removed from gene: LTBP3. Tag Q1_22_MOI was removed from gene: LTBP3.
Mode of inheritance for gene LTBP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LTBP3 were changed from Geleophysic dysplasia 3 617809; Dental anomalies and short stature 610216; Geleophysic dysplasia 3 617809 to Geleophysic dysplasia 3, OMIM:617809; Dental anomalies and short stature, OMIM:610216; geleophysic dysplasia 3, MONDO:0054722,
Publications for gene: LTBP3 were set to 27068007
Mode of inheritance for gene: LTBP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tag Q1_22_NHS_review tag was added to gene: LTBP3. Tag Q1_22_MOI tag was added to gene: LTBP3.
Added phenotypes Dental anomalies and short stature 610216; Geleophysic dysplasia 3 617809 for gene: LTBP3
Source NHS GMS was added to LTBP3. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for LTBP3 were set to Geleophysic dysplasia 3 617809
This gene has been classified as Green List (High Evidence).
LTBP3 was added to Unexplained skeletal dysplasia panel. Sources: Literature
LTBP3 was created by Sarah Leigh