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- Title
A founder DBR1 variant causes a lethal form of congenital ichthyosis.
- Authors
Shamseldin, Hanan E.; Sadagopan, Mukunth; Martini, Javier; Al-Ali, Ruslan; Radefeldt, Mandy; Ataei, Mojgan; Lemke, Sabrina; Rahbeeni, Zuhair; Al Mutairi, Fuad; Ababneh, Faroug; AlRukban, Hadeel A.; Abdulwahab, Firdous; Alhajj, Saleh Mohammed; Bauer, Peter; Bertoli-Avella, Aida; Alkuraya, Fowzan S.
- 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.
- Subjects
PULLULANASE; ICHTHYOSIS; FETAL development; ENZYME deficiency; ENCEPHALITIS
- Publication
Human Genetics, 2023, Vol 142, Issue 10, p1491
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-023-02597-3