title: Single-nucleotide polymorphism array-based characterization of ring chromosome 18.
abstract: OBJECTIVE
  To study genotype-phenotype correlation of ring chromosome 18 [r(18)] in 9 patients with 46,XN karyotype.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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-.
authors.affiliation: Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Spreiz
authors.forename: Roberta S
authors.initials: RS
authors.lastname: Guilherme
authors.forename: Claudio
authors.initials: C
authors.lastname: Castellan
authors.forename: Andrew
authors.initials: A
authors.lastname: Green
authors.forename: Olaf
authors.initials: O
authors.lastname: Rittinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wellek
authors.forename: Barbara
authors.initials: B
authors.lastname: Utermann
authors.forename: Martin
authors.initials: M
authors.lastname: Erdel
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Chong A
authors.initials: CA
authors.lastname: Kim
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Kulikowski
authors.forename: Vera A
authors.initials: VA
authors.lastname: Meloni
authors.forename: Gerd
authors.initials: G
authors.lastname: Utermann
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Maria I
authors.initials: MI
authors.lastname: Melaragno
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
mesh_terms: D000293:Adolescent; D000328:Adult; D049628:Body Size; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000648:ultrastructure; D005260:Female; D056726:Genetic Association Studies; D006257:Head / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008423:Maternal Age; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012303:Ring Chromosomes; D055815:Young Adult
keywords: OFC; Occipitofrontal head circumference; Ring chromosome; SNP; Single-nucleotide polymorphism; r(18)