title: A girl with deletion 9q22.1-q22.32 including the PTCH and ROR2 genes identified by genome-wide array-CGH.
abstract: The underlying genetic cause of mental retardation (MR) remains unknown in about half of the cases. Recently, using whole genome array comparative genomic hybridization (array-CGH), submicroscopic genetic imbalances have been detected in up to 20% of patients with an unexplained MR, dysmorphic features, and apparently normal karyotype. Here, we present a 12-year-old girl with features of basal cell nevus syndrome (BCNS), pulmonary valve stenosis, and MR, in whom array-CGH identified a 7.7 Mb deletion on 9q22.1-q22.32. The deleted region includes, among others, the ROR2 and PTCH genes. Haploinsufficiency of PTCH causes the BCNS syndrome and mutations in ROR2 have been found in an autosomal recessive Robinow syndrome and a dominantly inherited brachydactyly type 1B. We speculate that haploinsufficiency of ROR2 may contribute to pulmonary valve stenosis. Because of an age-dependent penetrance, BCNS may be challenging for diagnosis particularly when the features are not part of a typical clinical spectrum of BCNS. Early diagnosis of BCNS is important for preventing the development of associated tumors and better care of the patient. Our data confirm the previous observations that application of the whole genome array-CGH should be considered in selected patients with undiagnosed MR and dysmorphic features.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland. bnowakowska@imid.med.pl
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Kutkowska-Kaźmierczak
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Ewa
authors.initials: E
authors.lastname: Bocian
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
authors.forename: Zhishuo
authors.initials: Z
authors.lastname: Ou
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Cai
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D001478:Basal Cell Nevus Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial; D002899:Chromosomes, Human, Pair 9; D019066:Facies; D005260:Female; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors