Limb disorders

Gene: TCTN2

Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.

Created: 2 Dec 2018, 11:11 p.m.

Comment on mode of inheritance: Biallelic MOI confirmed by OMIM and Gene2Phenotype.

Created: 15 Oct 2018, 3:04 p.m.

Comment when marking as ready: 2 cases of polydactyl in literature plus mouse model.

Created: 11 Oct 2018, 3:58 p.m.

Comment on list classification: Updated rating from Red to Green: 2 cases of polydactyly in literature as part of Joubert syndrome (PMID:25118024) and Meckel-Gruber syndrome (PMID:21462283) PLUS mouse model of polydactyly (PMID:21565611).

Created: 11 Oct 2018, 3:57 p.m.

Sang et al (2011, PMID:21565611) report a mouse model of Tctn2-/- embryos that exhibit defects including single hindlimb preaxial polydactyly, either bilaterally or unilaterally.

Created: 11 Oct 2018, 3:51 p.m.

In affected members of a consanguineous Arab family with Meckel-Gruber syndrome, Shaheen et al. (2011, PMID:21462283) identified homozygosity for a splice site mutation in the TCTN2 gene (1506-2A-G). Phenotypes included polydactyly in all recorded patients.

Created: 11 Oct 2018, 3:50 p.m.

Huppke et al. (2015, PMID:25118024) reported a 7.5-year-old Turkish boy, born of consanguineous parents, with a neurodevelopmental disorder consistent with Joubert syndrome. At birth, the patient was noted to have postaxial hexadactyly of all 4 extremities. The authors identified a homozygous splice site mutation in the TCTN2 gene (c.1235-1G-A, NM_024809.4). The unaffected mother was heterozygous for the variant.

Created: 11 Oct 2018, 3:46 p.m.

Additional variable features of Joubert Syndrome include postaxial polydactyly. Meckel-Gruber syndrome (MGS) is a severe autosomal recessive ciliopathy classically defined by the triad of encephalocele, polydactyly, and renal and biliary ductal dysplasia.

Created: 11 Oct 2018, 3:45 p.m.