The TCTN2 gene encodes a type I membrane protein that belongs to the tectonic family. This gene is expressed in all tissues, with significant expression in brain, kidney, and eye. Studies in mice suggest that this protein may be involved in hedgehog signaling, and is essential for ciliogenesis.
Mutations in this gene are associated with Meckel syndrome type 8 and Joubert syndrome type 24.
The TCTN2 gene is located on the long (q) arm of chromosome 12 at position 24.31. It spans 37,293 bases and contains 18 exons. The deduced mouse Tctn2 protein contains 700 amino acids. It has an N-terminal signal peptide and a C-terminal transmembrane domain that is conserved in Drosophila tectonic. A splice site mutation in the TCTN2 gene was identified in one family. Different homozygous mutations in the TCTN2 gene have been identified as well.
Shaheen et al. (2011) studied a consanguineous family of Arab origin affected with Meckel Syndrome. Homozygosity scan in the first family revealed the presence of only one overlapping ROH of 7Mb in size on chromosome 12. A splice site mutation (c.1506_2A4G; NM_024809.3) in the TCTN2 gene was identified in this family, which was is predicted in silico to fully abolish the original acceptor. This mutation was found to segregate with the disease in the family and was not observed in 192 ethnically matched controls. This defined TCTN2 as a novel MKS locus.
Al-Hamed et al. (2016) carried out a study of antenatal cystic kidney disease in a cohort of 44 Saudi families. Genetic screening of 90 renal genes helped uncover a novel homozygous mutation in the TCTN2 gene of one proband. The patient suffered from enlarged echogenic kidneys, encephalocele and micrognathia, resulting in perinatal death. The nonsense mutation (c.1852C>T, p.Q618*) was predicted by ‘Mutation Taster’ to be disease causing. In another family, antenatal ultrasound found cystic kidneys. The case resulted in fetal death and DNA was unavailable for analysis. However, the consanguineous parents were both found to be heterozygous for the novel TCTN2 mutation c.252_253delTG (p.V85Dfs*24). This frameshift mutation was also predicted by ‘Mutation Taster’ to be disease causing. Both TCTN2 mutations occurred at residues conserved from humans to X. tropicalis and were absent from the ExAC database.
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