A founder DBR1 variant causes a lethal form of congenital ichthyosis

We describe a distinct allelic disorder caused by a founder recessiveDBR1 variant in four families (DBR1(NM_016216.4):c.200A  >  G (p.Tyr67Cys)). Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. Patient-derived fibroblasts displayed the characteristic accumul ation of intron lariats in their RNA as revealed by targeted and untargeted analysis, in addition to a marked reduction of DBR1 on immunoblot analysis. We propose a novelDBR1-related developmental disorder that is distinct fromDBR1-related encephalitis susceptibility and highlight the apparent lack of correlation with the degree of DBR1 deficiency.
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research