A founder DBR1 variant causes a lethal form of congenital ichthyosis.

Abstract

DBR1 encodes the only known human lariat debranching enzyme and its deficiency has been found to cause an autosomal recessive inborn error of immunity characterized by pediatric brainstem viral-induced encephalitis (MIM 619441). We describe a distinct allelic disorder caused by a founder recessive DBR1 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 accumulation 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 novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility and highlight the apparent lack of correlation with the degree of DBR1 deficiency.

• Authors: Hanan E Shamseldin, Mukunth Sadagopan, Javier Martini, Ruslan Al-Ali, Mandy Radefeldt, Mojgan Ataei, Sabrina Lemke, Zuhair Rahbeeni, Fuad Al Mutairi, Faroug Ababneh, Hadeel A AlRukban, Firdous Abdulwahab, Saleh Mohammed Alhajj, Peter Bauer, Aida Bertoli-Avella, Fowzan S Alkuraya
• Journal: Human genetics (Hum Genet) Vol. 142 Issue 10 Pg. 1491-1498 (Oct 2023) ISSN: 1432-1203 [Electronic] Germany
• PMID: 37656279 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Dbr1 protein, human

Topics

• Child
• Humans
• Alleles
• Causality
• Encephalitis
• Fibroblasts
• Ichthyosis (genetics)