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Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease.
Ital J Pediatr. 2019 Apr 18; 45(1):49.IJ

Abstract

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.

Links

Authors+Show Affiliations

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

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

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

Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

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

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

Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

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

MeSH

AdultExonsFemaleHirschsprung DiseaseHomeodomain ProteinsHumansHypoventilationInfantMaleMutationSleep Apnea, CentralTranscription Factors

Pub Type(s)

Case Reports

Journal Article

Language

eng

PubMed ID

30999961

Citation

Paglietti, Maria Giovanna, et al. "Two Novel Mutations in Exon 3 of PHOX2B Gene: Think About Congenital Central Hypoventilation Syndrome in Patients With Hirschsprung Disease." Italian Journal of Pediatrics, vol. 45, no. 1, 2019, p. 49.

Paglietti MG, Cherchi C, Porcaro F, et al. Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease. Ital J Pediatr. 2019;45(1):49.

Paglietti, M. G., Cherchi, C., Porcaro, F., Agolini, E., Schiavino, A., Petreschi, F., Novelli, A., & Cutrera, R. (2019). Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease. Italian Journal of Pediatrics, 45(1), 49. https://doi.org/10.1186/s13052-019-0636-8

Paglietti MG, et al. Two Novel Mutations in Exon 3 of PHOX2B Gene: Think About Congenital Central Hypoventilation Syndrome in Patients With Hirschsprung Disease. Ital J Pediatr. 2019 Apr 18;45(1):49. PubMed PMID: 30999961.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease. AU - Paglietti,Maria Giovanna, AU - Cherchi,Claudio, AU - Porcaro,Federica, AU - Agolini,Emanuele, AU - Schiavino,Alessandra, AU - Petreschi,Francesca, AU - Novelli,Antonio, AU - Cutrera,Renato, Y1 - 2019/04/18/ PY - 2018/09/19/received PY - 2019/03/29/accepted PY - 2019/4/20/entrez PY - 2019/4/20/pubmed PY - 2019/8/21/medline KW - C.255_256delCT KW - C.780dupT KW - Congenital central hypoventilation syndrome KW - Genotype-fenotype correlation KW - NPARMs KW - PHOX2B gene SP - 49 EP - 49 JF - Italian journal of pediatrics JO - Ital J Pediatr VL - 45 IS - 1 N2 - 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. SN - 1824-7288 UR - https://www.unboundmedicine.com/medline/citation/30999961/Two_novel_mutations_in_exon_3_of_PHOX2B_gene:_think_about_congenital_central_hypoventilation_syndrome_in_patients_with_Hirschsprung_disease_ DB - PRIME DP - Unbound Medicine ER -