A new nonsense pathogenic variant in exon 1 of PHOX2B leads to the diagnosis of congenital central hypoventilation syndrome with intra-familial variability.
Arch Pediatr
; 2024 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-39261201
ABSTRACT
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system resulting in decreased brain sensitivity to hypercapnia and hypoxia characterized by a genetic abnormality in the pair-like homeobox 2B (PHOX2B) gene. Most patients have a heterozygous expansion of the polyalanine repeat in exon 3 (PARM), while 10 % of patients have non-PARM (NPARM) mutations that can span the entire gene. The majority of pathogenic variants are de novo, but variants with incomplete penetrance can be identified in the heterozygous state. In the present report, CCHS was diagnosed in a symptomatic 3-month-old infant with neonatal respiratory distress. Genetic analysis revealed a new mutation in exon 1 of the PHOX2B gene - p.Ser28* (c.83C>G) - which was further identified in two family members, one minimally symptomatic and one asymptomatic. The identification of this new mutation supports the importance of sequencing the entire gene even when the classic PARM mutation is not found and highlights the phenotypic variability of CCHS.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Arch Pediatr
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Francia