title Novel mutation in the i CLDN1 i gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis NISCH syndrome title

İngilizce (OpenAlex)

P.K. and E.S. contributed equally to this work. Funding sources: This study was supported by the Institute of Human Genetics at the University Medical Center Freiburg. I.H. was supported by a BMBF grant NIRK 016GM0904 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflicts of interest: No conflicts of interest to disclose. Dear Editor, Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome (MIM #607626) also known as ichthyosis–hypotrichosis–sclerosing cholangitis (IHSC)1 is a rare autosomal recessive disorder characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. Additional clinical features include hair and teeth anomalies and in individual cases, mental retardation and bilateral uveal synechiae.2 3 NISCH syndrome is caused by mutations in the CLDN1 gene (MIM *603718) that encodes the tight junction protein claudin‐1.4 A lack of claudin‐1 leads to increased paracellular permeability between epithelial cells.4 5 Only two homozygous mutations (c.200delTT and c.358delG)3 4 in the CLDN1 gene have been reported in 12 patients from five families with NISCH syndrome to date.6 Here we describe two patients from a consanguineous family of Turkish origin with the clinical characteristics of NISCH syndrome who harbour a novel homozygous nonsense mutation in the CLDN1 gene (c.181C>T, p.Gln61X), which leads to a truncated protein.