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Analysis of RET , ZEB2 , EDN3 and GDNF Genomic Rearrangements in Central Congenital Hyperventilation Syndrome Patients by Multiplex Ligation‐dependent Probe Amplification
Author(s) -
Serra Alexandre,
Görgens Heike,
Alhadad Karin,
Fitze Guido,
Schackert Hans K.
Publication year - 2010
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2010.00577.x
Subject(s) - multiplex ligation dependent probe amplification , congenital central hypoventilation syndrome , genetics , glial cell line derived neurotrophic factor , biology , gene , medicine , exon , hypoventilation , respiratory system , receptor , neurotrophic factors
Summary Central congenital hypoventilation syndrome (CCHS) is an autonomous control disease producing hypoventilation, high PaCO 2 , and low PaO 2 during quiet sleep. The main gene variants detected in CCHS are mutations in the PHOX2b gene in up to 97% of isolated cases. However, CCHS is sometimes associated with autonomic diseases such as Hirschsprung disease (HSCR). Since genomic rearrangements in particularly sensitive areas of the RET protooncogene and/or associated genes may account for the CCHS/HSCR phenotype in patients without other detectable RET variants, the aim of the present study was to identify rearrangements in the coding sequence of RET as well as in three HSCR‐associated genes ( ZEB2 , EDN3 and GDNF ) in CCHS/HSCR patients by using Multiplex Ligation‐dependent Probe Amplification (MLPA). We have screened 27 CCHS and 11 CCHS/HSCR patients for genomic rearrangements in RET, ZEB2, EDN3 and GDNF and did not identify any deletion or amplification in these four genes in all patients. We conclude that genomic rearrangements in RET are rare and were not responsible for the CCHS/HSCR phenotype in individuals without identifiable germline RET variants in our group of patients, yet this possibility cannot be excluded altogether given the size of the cohort.