Single-Nucleotide Polymorphism Array-Based Characterization of Ring Chromosome 18

Objective To study genotype-phenotype correlation of ring chromosome 18 [r(18)] in 9 patients with 46, XN karyotype. Study design in 9 patients with a de novo 46, XN, r(18) karyotype (7 females, 2 males), we performed high-resolution single-nucleotide polymorphism array analysis (Illumina Human Omni1-QuadV1 array in 6 patients, Affymetrix 6.0 array in 3 patients), investigation of parental origin, and genotype-phenotype correlation. Results No breakpoint was recurrent. Single metaphases with loss of the ring, double rings, or secondarily rearranged rings were found in some cases, but true mosaicism was present in none of these cases. in 3 patients, additional duplications in 18p (of 1.4 Mb, 2 Mb, and 5.8 Mb) were detected. in 1 patient, an additional deletion of 472 kb in Xp22.33, including the SHOX gene, was found. Parental origin of r(18) was maternal in 2 patients and paternal in 4 patients, and formation was most likely meiotic. Karyotype was normal in all investigated parents (n = 15). At birth, mean maternal age was 30 years (n = 9) and mean paternal age was 34.4 years (n = 9). Conclusion Genotype-phenotype correlation revealed extensive clinical variability but no characteristic r(18) phenotype. Severity of clinical signs were generally correlated with the size of the deletion. Patients with large deletions in 18p and small deletions in 18q exhibited mainly symptoms related to 18p-, whereas those with large deletions in 18q and small deletions in 18p had symptoms of 18q-.Oesterreichische Nationalbank (Anniversary Fund)Medizinischer Forschungsfond InnsbruckFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Med Univ Innsbruck, Dept Med Genet, Div Human Genet, A-6020 Innsbruck, AustriaUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilGen Reg Hosp, Dept Pediat, Clin Genet Serv, Bolzano, ItalyOur Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, IrelandParacelsus Med Univ, Dept Pediat, Salzburg, AustriaJohannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Human Genet, D-55122 Mainz, GermanyMed Univ Innsbruck, Clin Dept Pediat 1, A-6020 Innsbruck, AustriaUniversidade de São Paulo, Fac Med, Childrens Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilUniversidade de São Paulo, Fac Med, Childrens Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Pathol, São Paulo, BrazilOesterreichische Nationalbank (Anniversary Fund): 12530Oesterreichische Nationalbank (Anniversary Fund): 13004Medizinischer Forschungsfond Innsbruck: 2007411FAPESP: 2010/50737-1Web of Scienc