title: Comparable low-level mosaicism in affected and non affected tissue of a complex CDH patient.
abstract: In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow-up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future.
authors.affiliation: Department of Pediatric Surgery, Erasmus-MC Sophia, Rotterdam, The Netherlands. d.veenma@erasmusmc.nl
authors.forename: Danielle
authors.initials: D
authors.lastname: Veenma
authors.forename: Niels
authors.initials: N
authors.lastname: Beurskens
authors.forename: Hannie
authors.initials: H
authors.lastname: Douben
authors.forename: Bert
authors.initials: B
authors.lastname: Eussen
authors.forename: Petra
authors.initials: P
authors.lastname: Noomen
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Govaerts
authors.forename: Els
authors.initials: E
authors.lastname: Grijseels
authors.forename: Maarten
authors.initials: M
authors.lastname: Lequin
authors.forename: Ronald
authors.initials: R
authors.lastname: de Krijger
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Dian
authors.initials: D
authors.lastname: Van Opstal
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D003582:Cytogenetics; D005260:Female; D006548:Hernia, Diaphragmatic / Q000175:diagnosis / Q000235:genetics; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009030:Mosaicism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA