title: Genotype/phenotype correlation in a female patient with 21q22.3 and 12p13.33 duplications.
abstract: Many chromosomal rearrangements that lead to copy-number gains or losses have been shown to cause distinctive and recognizable clinical phenotypes. Conventional cytogenetic analysis can detect many, but not all, rearrangements depending on its power of resolution. The wide use of whole-genome array-based comparative genomic hybridization (array-CGH) techniques has allowed the detection of novel syndromes and to establish genotype-phenotype correlations by delineating at high resolution the regions involved in specific chromosomal aberrations. We report on a two and half-year-old female patient with intellectual disability and distinctive phenotypic features resulting from a de novo duplication of about 0.3 Mb in 21q22.3 associated with duplication of about 0.3 Mb in 12p13.33. The patient's chromosomal abnormalities were identified at the cytogenetic molecular level, using SNP array analysis, while GTG banding technique revealed a normal karyotype. Clinical findings of the patient were compared with Down syndrome and 12p duplication syndrome. This study suggests that an area of contiguous genes on the distal part of chromosome 21 (21q22.3) contribute to the Down syndrome phenotype and indicates that genes in the distal region of 12p (12p13.33) account for many facial characteristics and hypotonia of trisomy 12p syndrome.
authors.affiliation: Division of Human Genetics and Genome Research, Department of Human Cytogenetics, National Research Centre, Cairo, Egypt.
authors.forename: Mona K
authors.initials: MK
authors.lastname: Mekkawy
authors.affiliation: Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
authors.forename: Inas M
authors.initials: IM
authors.lastname: Mazen
authors.affiliation: Division of Human Genetics and Genome Research, Department of Human Cytogenetics, National Research Centre, Cairo, Egypt.
authors.forename: Alaa K
authors.initials: AK
authors.lastname: Kamel
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.affiliation: Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
authors.forename: Maha S
authors.initials: MS
authors.lastname: Zaki
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D056915:DNA Copy Number Variations; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014314:Trisomy
keywords: 12p duplication syndrome; Down syndrome critical region; microarray; subtelomeric rearrangements