Skeletal ciliopathies

Gene: TCTEX1D2

Added new-gene-name tag, new approved HGNC gene symbol for TCTEX1D2 is DYNLT2B

Created: 23 Feb 2021, 5:55 p.m. | Last Modified: 23 Feb 2021, 5:55 p.m.

Panel Version: 1.10

Comment on list classification: Updated rating from Grey to Green. 2 Green reviews plus sufficient unrelated cases of ciliogenesis phenotypes (PMIDs:26044572, 28475963). Role in ciliogenesis supported by functional assays and zebrafish model (PMID:26044572).

Created: 16 Oct 2018, 3:13 p.m.

Zebrafish ciliopathy model demonstrated in PMID:26044572 and functional evidence that loss of TCTEX1D2 impairs retrograde intraflagellar transport in humans.

Created: 16 Oct 2018, 3:11 p.m.

PMID:26044572 (Schmidts et al 2015) performed whole exome sequencing of 69 individuals from 60 families clinically diagnosed with JATD, and identified a homozygous consensus splice variant (c.113+2C>G) in TCTEX1D2 from a consanguineous Turkish family. Additional analysis of further JATD/SRPS cases found a compound heterozygous TCTEX1D2 variant in a non-consanguineous French family comprising a nonsense (c.262C>T; p.Arg88*) and a deletion-insertion frameshift (c.100delinsCT; p.Val34Leufs*12).

The authors also identified a >10-kb homozygous deletion in two affected siblings (UCL4 II.6 and II.8) from a consanguineous Arabic family that removes exon 1–2 of TCTEX1D2 (plus exons from neighbouring TM4SF19 gene). The deletion was also detected in 2 apparently unaffected sibs, indicating reduced penetrance.

Created: 16 Oct 2018, 3:11 p.m.

Zschocke et al 2017 (PMID:28475963) identified two siblings from a consanguineous Turkish family with defects suggestive of ciliary dysfunction (the girl who died in utero likely had Jeune syndrome). Exome sequencing identified a homozygous intragenic deletion in TCTEX1D2. Ciliary function tests showed mild irregulatories of motile cilia.

Created: 16 Oct 2018, 3:06 p.m.

Comment on mode of inheritance: Biallelic MOI supported by OMIM.

Created: 16 Oct 2018, 2:57 p.m.

Green List (high evidence)

25830415 provides functional evidence of the role of this gene in ciliogenesis. 3 families in two different papers (26044572; 28475963) with loss of function recessive mutations in TCTEX1D2 and Jeune syndrome or other skeletal dysplasia.

Created: 16 Sep 2018, 7:31 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Jeune asphyxiating thoracic dystrophy; short ribs; polydactyly

Publications

• 25830415
• 26044572
• 28475963

Green List (high evidence)

Three unrelated families reported, functional evidence.

Created: 7 Aug 2018, 5:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Jeune ATD

Publications

• 26044572

Variants in this GENE are reported as part of current diagnostic practice