Ehlers Danlos syndrome with a likely monogenic cause
Gene: LTBP1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.Created: 1 Feb 2023, 4:19 p.m. | Last Modified: 1 Feb 2023, 4:19 p.m.
Panel Version: 2.68
Comment on list classification: Promoting from grey to amber with a recommendation for green rating following GMS review. 3 families reported where joint hyperlaxity is noted.Created: 28 Jul 2021, 2:40 a.m. | Last Modified: 28 Jul 2021, 2:40 a.m.
Panel Version: 2.63
Associated with Cutis laxa, autosomal recessive, type IIE #619451 (AR) in OMIM.
As expert reviewer reports PMID: 33991472 - Pottie et al 2021 - report 8 individuals from 4 unrelated consanguineous families with 4 different homozygous premature truncating LTBP1 variants. Core clinical features include cutis laxa, craniosynostosis, a copper beaten calvarium, short stature, and discernible craniofacial characteristics. Joint hyperlaxity is noted in 4/8 (50%) individuals from 3 of the families. Supportive zebrafish model.Created: 28 Jul 2021, 2:36 a.m. | Last Modified: 28 Jul 2021, 2:36 a.m.
Panel Version: 2.60
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cutis laxa, autosomal recessive, type IIE, OMIM:619451; Joint hyperlaxity
Publications
Based on the literature homozygous premature truncating LTBP1 variants was reported in eight affected individuals with connective tissue features. In vivo validation with two independent zebrafish lines carrying mutations in LTBP1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae.
Sources: LiteratureCreated: 14 Jun 2021, 10:46 a.m. | Last Modified: 14 Jun 2021, 10:49 a.m.
Panel Version: 2.57
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cutis laxa; Craniofacial dysmorphism; Altered skeletal development, including short stature; Brachydactyly; Clinodactyly
Publications
Tag Q3_21_rating was removed from gene: LTBP1.
Gene: ltbp1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: LTBP1 were changed from Cutis laxa; craniofacial dysmorphism; altered skeletal development, including short stature; brachydactyly; clinodactyly to Cutis laxa, autosomal recessive, type IIE, OMIM:619451; Joint hyperlaxity
Publications for gene: LTBP1 were set to PMID: 33991472
Tag Q3_21_rating tag was added to gene: LTBP1.
gene: LTBP1 was added gene: LTBP1 was added to Ehlers Danlos syndromes. Sources: Literature Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP1 were set to PMID: 33991472 Phenotypes for gene: LTBP1 were set to Cutis laxa; craniofacial dysmorphism; altered skeletal development, including short stature; brachydactyly; clinodactyly Penetrance for gene: LTBP1 were set to Complete Review for gene: LTBP1 was set to GREEN