Skeletal dysplasia
Gene: TMEM251Added new-gene-name tag, new approved HGNC gene symbol for TMEM251 is LYSET.
The OMIM entry for this gene is OMIM:619332, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.Created: 17 Oct 2023, 11:49 a.m. | Last Modified: 17 Oct 2023, 11:49 a.m.
Panel Version: 4.23
Comment on list classification: Promoting from grey to amber. 2 cases reported.Created: 20 Oct 2021, 10:40 a.m. | Last Modified: 20 Oct 2021, 10:40 a.m.
Panel Version: 2.139
Associated with Dysostosis multiplex, Ain-Naz type #619345 (AR) in OMIM.
As reviewer states, PMID:33252156 (Ain et al 2021), reports two unrelated families (from Pakistan and Iran) with individuals presenting with a severe skeletal disorder. WES identified two homozygous variants (missense and nonsense) in TMEM251. The candidate variants segregated with 5 affected members of the first family. In the second family there was only 1 affected individual who was homozygous for the variant, 22 other unaffected members were either heterozygous or and wild type alleles. The affected patient from the second family had developmental delay and craniosynostosis in addition to skeletal abnormalities. Abnormal activities of three lysosomal enzymes detected from the sample of the patient from one family suggest that TMEM251 may have a metabolic role. (It was not possible to perform these tests in affected individuals in the other family). Some functional data (p.Arg45Trp mutant TMEM251 protein was targeted less efficiently and the localization was punctate in Golgi in osteosarcoma cells, and Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes).Created: 20 Oct 2021, 10:32 a.m. | Last Modified: 20 Oct 2021, 10:32 a.m.
Panel Version: 2.137
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dysostosis multiplex, Ain-Naz type, OMIM:19345
Publications
Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes.
Sources: LiteratureCreated: 21 Jan 2021, 9:19 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dysostosis multiplex‐like skeletal dysplasia; severe short stature
Publications
Tag new-gene-name tag was added to gene: TMEM251. Tag gene-checked tag was added to gene: TMEM251.
Gene: tmem251 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type, OMIM:19345; severe short stature
gene: TMEM251 was added gene: TMEM251 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM251 were set to 33252156 Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature Review for gene: TMEM251 was set to AMBER