Two novel mutations in exon 3 of PHOX2B gene

think about congenital central hypoventilation syndrome in patients with Hirschsprung disease

Maria Giovanna Paglietti, Claudio Cherchi, Federica Porcaro, Emanuele Agolini, Alessandra Schiavino, Francesca Petreschi, Antonio Novelli, Renato Cutrera

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)49
JournalItalian Journal of Pediatrics
Volume45
Issue number1
DOIs
Publication statusPublished - Apr 18 2019

Fingerprint

Hirschsprung Disease
Exons
Mutation
Genes
Sleep
Hypoventilation
Pulmonary Medicine
Hypercapnia
Congenital central hypoventilation syndrome
Arousal
Alanine
Italy
Ventilation
Pediatrics
Phenotype

Cite this

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title = "Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease",
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 Ges{\`u} 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.",
author = "Paglietti, {Maria Giovanna} and Claudio Cherchi and Federica Porcaro and Emanuele Agolini and Alessandra Schiavino and Francesca Petreschi and Antonio Novelli and Renato Cutrera",
year = "2019",
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day = "18",
doi = "10.1186/s13052-019-0636-8",
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pages = "49",
journal = "Italian Journal of Pediatrics",
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TY - JOUR

T1 - Two novel mutations in exon 3 of PHOX2B gene

T2 - 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

PY - 2019/4/18

Y1 - 2019/4/18

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.

AB - 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.

U2 - 10.1186/s13052-019-0636-8

DO - 10.1186/s13052-019-0636-8

M3 - Article

VL - 45

SP - 49

JO - Italian Journal of Pediatrics

JF - Italian Journal of Pediatrics

SN - 1720-8424

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