- 作者：Ana Spreiz ; Roberta S. Guilherme ; Claudio Castellan ; Andrew Green ; Olaf Rittinger ; Brigitte Wellek ; Barbara Utermann ; Martin Erdel ; Christine Fauth ; Edda Haberl ; t ; Chong A. Kim ; Leslie D. Kulikowski ; Vera A. Meloni ; Gerd Utermann ; Johannes Zschocke ; Maria I. Melaragno ; Dieter Kotzot
- 关键词：OFC ; Occipitofrontal head circumference ; r(18) ; Ring chromosome ; SNP ; Single-nucleotide polymorphism
- 刊名：The Journal of Pediatrics
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：163
- 期：4
- 页码：1174-1178.e3
- 全文大小：964 K
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-.