Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: Delineation of the critical region for a consensus phenotype.
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.
Swinkels
Mariëlle E M
ME
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen Centre of Molecular Life Sciences, Nijmegen, The Netherlands.
Simons
Annet
A
Smeets
Dominique F
DF
Vissers
Lisenka E
LE
Veltman
Joris A
JA
Pfundt
Rolph
R
de Vries
Bert B A
BB
Faas
Brigitte H W
BH
Schrander-Stumpel
Connie T R M
CT
McCann
Emma
E
Sweeney
Elizabeth
E
May
Paul
P
Draaisma
Jos M
JM
Knoers
Nine V
NV
van Kessel
Ad Geurts
AG
van Ravenswaaij-Arts
Conny M A
CM
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
C514249:CER1 protein, human; D016207:Cytokines