Thoracic aortic aneurysm and dissection

Gene: LTBP3

Amber List (moderate evidence)

LTBP3 (latent transforming growth factor beta binding protein 3)
EnsemblGeneIds (GRCh38): ENSG00000168056
EnsemblGeneIds (GRCh37): ENSG00000168056
OMIM: 602090, Gene2Phenotype
LTBP3 is in 8 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: Note monoallelic variants in this gene have also been reported in association with Geleophysic dysplasia 3 but a cardiac phenotype is not noted in these cases to date.
Created: 2 Mar 2022, 6:44 p.m. | Last Modified: 2 Mar 2022, 6:44 p.m.
Panel Version: 1.21
Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for GREEN rating following GMS review.
Created: 2 Mar 2022, 6:41 p.m. | Last Modified: 2 Mar 2022, 6:41 p.m.
Panel Version: 1.20
As reported by Tracy Lester there are now 3 families reported with valvular and/or vascular defects as well as dental abnormalities and short stature:

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 prolaps

PMID: 29625025 - Guo et al 2018 - report 2 families with individuals presenting with dental abnormalities and short stature and aneurysms and dissections of the thoracic aorta, aneurysms of the abdominal aorta and other arteries, and dental abnormalities and short stature. In one family compound heterozygous variants segregated with the disease and in the other a homozygous variant was found in all affected individuals. All the individuals with biallelic variants needed treatment before the age of 45. Heterozygous carriers of the p.Asn678_Gly681delinsThrCys variant have later onset of thoracic aortic disease, as well as dental abnormalities.
Created: 2 Mar 2022, 6:40 p.m. | Last Modified: 2 Mar 2022, 6:40 p.m.
Panel Version: 1.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dental anomalies and short stature, OMIM:601216

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR Short stature with dental anomalies (MIM601216) is an autosomal recessive disorder that can present with variable valvular and/or vascular defects, including mitral valve prolapse, aortic root dilation, and aortic as well as other arterial aneurysms. Pathogenic variant was alsmost missed as it was not tiered - not green on this panel and gene was on skeletal panel with only monoallelic mode of inheritance.
Sources: NHS GMS
Created: 14 Feb 2022, 10:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short stature; dental anomalies; aortopathy; facial dysmorphism; learning disability

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Short stature
  • dental anomalies
  • aortopathy
  • facial dysmorphism
  • learning disability
  • Dental anomalies and short stature, OMIM:601216
Tags
Q1_22_rating
OMIM
602090
Clinvar variants
Variants in LTBP3
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

2 Mar 2022, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: LTBP3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

2 Mar 2022, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q1_22_rating tag was added to gene: LTBP3.

2 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: ltbp3 has been classified as Amber List (Moderate Evidence).

2 Mar 2022, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: LTBP3 were changed from Short stature; dental anomalies; aortopathy; facial dysmorphism; learning disability to Short stature; dental anomalies; aortopathy; facial dysmorphism; learning disability; Dental anomalies and short stature, OMIM:601216

14 Feb 2022, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Tracy Lester (Genetics laboratory, Oxford UK)

gene: LTBP3 was added gene: LTBP3 was added to Thoracic aortic aneurysm and dissection. Sources: NHS GMS Mode of inheritance for gene: LTBP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP3 were set to 25899461; 29625025 Phenotypes for gene: LTBP3 were set to Short stature; dental anomalies; aortopathy; facial dysmorphism; learning disability Penetrance for gene: LTBP3 were set to unknown