Skeletal dysplasia

Gene: TOPORS

Red List (low evidence)

Comment on list classification: There are 4 probands reported in literature with Joubert syndrome and the same homozygous missense variant in TOPORS (p.Pro10Gln). All 4 individuals are of Dominican ancestry. Hence, this is likely a founder allele. Also, the Joubert syndrome presentation is more appropriate for the Skeletal ciliopathies panel. Hence, this gene should be rated Red on Skeletal dysplasia. A founder-efffect tag was added.

Created: 3 Nov 2026, 11:36 a.m. | Last Modified: 3 Nov 2026, 11:39 a.m.

Panel Version: 10.32

PMID: 40358237 Lob & Brown, 2025
Report of a 12-month-old Dominican boy with a Dandy-Walker malformation (DWM, anomaly of cerebellar development), trigeminal neuralgia, molar tooth sign, mesoaxial polydactyly of hands and feet, hypotonia, and developmental delay. He was diagnosed with OFDS VI / Joubert syndrome. He was homozygous for TOPORS: c.29 C>A, p.Pro10Gln.

PMID: 37227088 Strong et al., 2023
Report of a proband of Dominican ancestry with Joubert syndrome. Exome seq showed he was homozygous for the c.29C>A, p.(Pro10Gln) variant in TOPORS.

PMID: 34132027 Strong et al., 2021
Study described two unrelated Dominican probands with oral cavity malformations, dysmorphic features, postaxial polydactyly, multiple lingual hamartomas, and dysmorphic features. Molar tooth sign also seen in Patient 2 - indicative of Joubert syndrome. Both patients were found to be homozygous for an identical TOPORS missense variant, c.29 C>A; (p.Pro10Gln). NO haplotype analysis. Variant may represent a Dominican Republic founder allele. 31 hets and no homozygotes reported in gnomAD v4.1.2. (MAF = 0.0001000, Admixed American pop).

TOPORS is not yet associated with a recessive disease entity in OMIM (heterozygous TOPORS variants between residues 807-867 are known to cause Retinitis pigmentosa 31) - OMIM accessed 3rd Nov 2026.

Created: 3 Nov 2026, 11:25 a.m. | Last Modified: 3 Nov 2026, 11:33 a.m.

Panel Version: 10.32

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome, MONDO:0018772

Publications

• 34132027
• 37227088
• 40358237