Tricho-Hepato-Enteric Syndromemutation update: Mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects

• Published in: Human mutation Vol. 39; no. 6; pp. 774 - 789
• Main Authors: Bourgeois, Patrice, Esteve, Clothilde, Chaix, Charlene, Béroud, Christophe, Levy, Nicolas, Fabre, Alexandre, Badens, Catherine, Consortium, Thes Clinical
• Format: Journal Article
• Language: English
• Published: Wiley 01.06.2018
• Subjects: Genetics; Human genetics; Life Sciences; Tricho-Hepato-Enteric Syndrome; TTC37; SKIV2L; intractable diarrhea; enteropathy
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.23418

Tricho-Hepato-Enteric syndrome (THES) is a very rare autosomal recessive syndromic enteropathy caused by mutations of either TTC37 or SKIV2L genes. Very little is known of these two gene products in mammals nor of the pathophysiology of the disease. Since the identification of the genes, we have set up the molecular diagnostic of THES in routine, gathering a large cohort with clinical and molecular data. Here, we report the phenotype and genotype analysis of this cohort together with an extensive literature review of THES cases worldwide, that is, 96 individuals harboring mutations in one gene or the other. We set up locus-specific databases for both genes and reviewed the type of mutation aswell as their localization in the proteins. No hot spot is evidenced for any type of mutation. The phenotypic analysis was first made on the whole cohort but is limited due to heterogeneity in clinical descriptions. We then examined the lab diagnostic cohort in detail for clinical manifestations. For the first time, we are able to suggest that patients lacking SKIV2L seem more severely affected than those lacking TTC37, in terms of liver damage and prenatal growth impairment.