title: Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: Delineation of the critical region for a consensus phenotype.
abstract: The deletion 9p syndrome is caused by a constitutional monosomy of part of the short arm of chromosome 9. It is clinically characterized by dysmorphic facial features (trigonocephaly, midface hypoplasia, and long philtrum), hypotonia and mental retardation. Deletion 9p is known to be heterogeneous and exhibits variable deletion sizes. The critical region for a consensus phenotype has been reported to be located within a approximately 4-6 Mb interval on 9p22. In the present study, deletion breakpoints were determined in 13 Dutch patients by applying fluorescence in situ hybridization (FISH) and in some specific cases by array-based comparative genomic hybridization (array CGH). No clear genotype-phenotype correlation could be established for various developmental features. However, we were able to narrow down the critical region for deletion 9p syndrome to approximately 300 kb. A functional candidate gene for trigonocephaly, the CER1 gene, appeared to be located just outside this region. Sequence analysis of this gene in nine additional patients with isolated trigonocephaly did not reveal any pathogenic mutations.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen Centre of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Mariëlle E M
authors.initials: ME
authors.lastname: Swinkels
authors.forename: Annet
authors.initials: A
authors.lastname: Simons
authors.forename: Dominique F
authors.initials: DF
authors.lastname: Smeets
authors.forename: Lisenka E
authors.initials: LE
authors.lastname: Vissers
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Brigitte H W
authors.initials: BH
authors.lastname: Faas
authors.forename: Connie T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
authors.forename: Emma
authors.initials: E
authors.lastname: McCann
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sweeney
authors.forename: Paul
authors.initials: P
authors.lastname: May
authors.forename: Jos M
authors.initials: JM
authors.lastname: Draaisma
authors.forename: Nine V
authors.initials: NV
authors.lastname: Knoers
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics*; D009426:Netherlands; D010641:Phenotype; D013577:Syndrome
chemical_list: C514249:CER1 protein, human; D016207:Cytokines