A founder DBR1 variant causes a lethal form of congenital ichthyosis.
Hum Genet
; 142(10): 1491-1498, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37656279
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encefalitis
/
Ictiosis
Tipo de estudio:
Etiology_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Hum Genet
Año:
2023
Tipo del documento:
Article
País de afiliación:
Arabia Saudita