Mutations in CRLF1 cause familial achalasia.
Clin Genet
; 92(1): 104-108, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-27976805
ABSTRACT
We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease-associated genes by a next-generation sequencing (NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1 (cytokine receptor-like factor 1). Mutations in CRLF1 have been associated with autosomal recessive Crisponi or cold-induced sweating syndrome type 1 (CS/CISS1), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC (p.Pro239Alafs*91) and the unaffected father carried the c.178T>A (p.Cys60Ser) variant. The c.713dupC variant has already been reported in affected CS/CISS1 patients, the pathogenicity of the c.178T>A variant was unclear. As reported previously for pathogenic CRLF1 variants, cytokine receptor-like factor 1 protein secretion from cells transfected with the c.178T>A variant was severely impaired. From these results we conclude that one should consider a CRLF1-related disorder in early onset achalasia even if other CS/CISS1 related symptoms are missing.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trismo
/
Anomalías Múltiples
/
Deformidades Congénitas de la Mano
/
Acalasia del Esófago
/
Receptores de Citocinas
/
Hiperhidrosis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Genet
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania