Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.
Clin Immunol
; 183: 17-23, 2017 10.
Article
in En
| MEDLINE
| ID: mdl-28668589
ABSTRACT
Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alternative Splicing
/
Fas Receptor
/
Autoimmune Lymphoproliferative Syndrome
Type of study:
Prognostic_studies
Limits:
Humans
/
Infant
/
Male
Country/Region as subject:
Africa
Language:
En
Journal:
Clin Immunol
Year:
2017
Document type:
Article