Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease.

Authors:
Maria Giovanna Paglietti
Maria Giovanna Paglietti
Bambino Gesu' Children's Research Hospital
Italy
Federica Porcaro
Federica Porcaro
Bambino Gesù Children's Hospital
MD
Rome | Italy
Emanuele Agolini
Emanuele Agolini
IRCCS-Casa Sollievo della Sofferenza Hospital
Italy
Alessandra Schiavino
Alessandra Schiavino
Università Cattolica Sacro Cuore
Italy
Francesca Petreschi
Francesca Petreschi
Bambino Gesù Children's Hospital
Roma | Italy
Antonio Novelli
Antonio Novelli
Bambino Gesù Pediatric Hospital
Italy
Renato Cutrera
Renato Cutrera
Bambino Gesù Children's Hospital
Italy

Ital J Pediatr 2019 Apr 18;45(1):49. Epub 2019 Apr 18.

Respiratory Unit, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio 4, 00165, Rome, Italy.

Background: Congenital central hypoventilation syndrome (CCHS) is characterized by alveolar hypoventilation increasing during sleep and affected patients are unable to perceive and respond to hypercarbia with increased ventilation and arousal during sleep. PHOX2B gene mutations are considered as responsible for CCHS. Most of patients with CCHS are heterozygous for polyalanine expansion mutations (PARMs) in exon 3, but 10% of patients with classic CCHS are heterozygous for non-polyalanine expansion mutations (NPARMs) of the PHOX2B gene.

Methods: Data are collected on 3 patients affected by CCHS who referred to the Paediatric Pulmonology Unit of Bambino Gesù Children's Hospital (Rome, Italy) for a multidisciplinary follow-up program between 2000 and 2017.

Results: We describe three cases of patients affected by CCHS for which two novel mutations on exon 3 of PHOX2B gene were detected.

Conclusions: The description of these novel mutations and related clinical phenotypes allows to expand the knowledge into NPARM spectrum. Since the presence of Hirschsprung disease is related to NPARMs and the number of alanine repeats, we suggest performing CCHS genetic investigation and periodical assessment also in patients without a clear history of CCHS but affected by Hirschsprung disease.

Trial Registration: Data are retrospectively collected.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13052-019-0636-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471850PMC
April 2019
6 Reads

Publication Analysis

Top Keywords

patients cchs
12
phox2b gene
12
novel mutations
12
cchs heterozygous
8
congenital central
8
central hypoventilation
8
expansion mutations
8
hirschsprung disease
8
cchs
8
mutations exon
8
hypoventilation syndrome
8
exon phox2b
8
patients
7
mutations
5
cchs referred
4
collected patients
4
genemethods data
4
data collected
4
genetic investigation
4
cchs genetic
4

References

(Supplied by CrossRef)
Article in Am Thorac Soc Am J Respir Crit Care Med
American Thoracic Society et al.
Am Thorac Soc Am J Respir Crit Care Med 1999
Article in Am J Respir Crit Care Med
DE Weese-Mayer et al.
Am J Respir Crit Care Med 2010
Article in J Appl Physiol (1985)
J Huang et al.
J Appl Physiol (1985) 2008
Article in Am J Med Genet A
DE Weese-Mayer et al.
Am J Med Genet A 2003
Article in Pediatr Pulmonol
DE Weese-Mayer et al.
Pediatr Pulmonol 2009
Article in Hum Mut
S Parodi et al.
Hum Mut 2008
Article in Nat Genet
J Amiel et al.
Nat Genet 2003
Article in Am J Respir Crit Care Med
EM Berry-Kravis et al.
Am J Respir Crit Care Med 2006
Article in Rev Mal Respir
DE Weese-Mayer et al.
Rev Mal Respir 2013
Article in Curr Opin Pediatr
MA Parisi et al.
Curr Opin Pediatr 2000
Article in Chest.
H Trang et al.
Chest. 2005

Similar Publications