Ciliopathies

Gene: TMEM216

Green List (high evidence)

PMID 39191256: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.

This included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.

Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.

Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.

Created: 5 Sep 2024, 1:29 a.m. | Last Modified: 5 Sep 2024, 1:29 a.m.

Panel Version: 1.58

p.Arg73Leu is a founder Jewish variant. Multiple families reported with JBTS and with Meckel syndrome.

Created: 27 Mar 2021, 2:28 a.m. | Last Modified: 27 Mar 2021, 2:28 a.m.

Panel Version: 0.263

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 2, MIM# 608091; Meckel syndrome 2, MIM# 603194; Retinitis pigmentosa, MONDO:0019200, TMEM216-related

Publications

• 20036350
• 20512146
• 39191256