title: A 600 kb triplication in the cat eye syndrome critical region causes anorectal, renal and preauricular anomalies in a three-generation family.
abstract: Cat eye syndrome (CES) is caused by a gain of the proximal part of chromosome 22. Usually, a supernumerary marker chromosome is present, containing two extra copies of the chromosome 22q11.1q11.21 region. More sporadically, the gain is present intrachromosomally. The critical region for CES is currently estimated to be about 2.1 Mb and to contain at least 14 RefSeq genes. Gain of this region may cause ocular coloboma, preauricular, anorectal, urogenital and congenital heart malformations. We describe a family in which a 600 kb intrachromosomal triplication is present in at least three generations. The copy number alteration was detected using MLPA and further characterized with interphase and metaphase FISH and SNP-array. The amplified fragment is located in the distal part of the CES region. The family members show anal atresia and preauricular tags or pits, matching part of the phenotype of this syndrome. This finding suggests that amplification of the genes CECR2, SLC25A18 and ATP6V1E1, mapping within the critical region for CES, may be responsible for anorectal, renal and preauricular anomalies in patients with CES.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Knijnenburg
authors.forename: Yolande
authors.initials: Y
authors.lastname: van Bever
authors.forename: Lorette O M
authors.initials: LO
authors.lastname: Hulsman
authors.forename: Chantal A P
authors.initials: CA
authors.lastname: van Kempen
authors.forename: Galhana M
authors.initials: GM
authors.lastname: Bolman
authors.forename: Rosa Laura E
authors.initials: RL
authors.lastname: van Loon
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Laura J C M
authors.initials: LJ
authors.lastname: van Zutven
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D027322:Amino Acid Transport System X-AG / Q000235:genetics*; D000782:Aneuploidy; D025063:Chromosome Disorders / Q000150:complications / Q000235:genetics*; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005124:Eye Abnormalities; D005190:Family; D005260:Female; D018628:Gene Dosage; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: D027322:Amino Acid Transport System X-AG; C576521:Cecr2 protein, human; D005819:Genetic Markers; D024101:Mitochondrial Proteins; C499216:SLC25A18 protein, human; D014157:Transcription Factors; C462522:ATP6V1E2 protein, human; D025262:Vacuolar Proton-Translocating ATPases