title: Definition of 5q11.2 microdeletion syndrome reveals overlap with CHARGE syndrome and 22q11 deletion syndrome phenotypes.
abstract: Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six patients with overlapping 5q11.2 deletions showed a phenotypic spectrum that overlaps with CHARGE syndrome and 22q11.2 deletion syndrome including choanal atresia, developmental delay, heart defects, external ear abnormalities, and short stature. No colobomas or abnormalities of semicircular canals and olfactory nerves were reported. Two male patients had genital abnormalities. We estimated a 2.0 Mb (53.0-55.0 Mb) Shortest Region of Overlap (SRO) for the main clinical characteristics of the syndrome. This region contains nine genes and two non-coding microRNAs. In this region DHX29 serves as the candidate gene as it encodes an ATP-dependent RNA-helicase that is involved in the initiation of RNA translation. Screening a small cohort of 14 patients who presented the main features, however, did not reveal any pathogenic abnormalities of DHX29.
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Snijders Blok
authors.forename: Nicole
authors.initials: N
authors.lastname: Corsten-Janssen
authors.forename: David R
authors.initials: DR
authors.lastname: FitzPatrick
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
authors.forename: Girolamo Aurelio
authors.initials: GA
authors.lastname: Vitello
authors.forename: Marjolein H
authors.initials: MH
authors.lastname: Willemsen
authors.forename: Jeroen
authors.initials: J
authors.lastname: Schoots
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
authors.forename: Lies
authors.initials: L
authors.lastname: Hoefsloot
authors.forename: Tjitske
authors.initials: T
authors.lastname: Kleefstra
mesh_terms: D058165:22q11 Deletion Syndrome / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D058747:CHARGE Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D055815:Young Adult
keywords: 22q11.2 deletion syndrome; 5q11.2 microdeletion syndrome; CHARGE syndrome; DHX29; choanal atresia; intellectual disability