Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications

Shino Shimada, Keiko Shimojima, Nobuhiko Okamoto, Noriko Sangu, Kyoko Hirasawa, Mari Matsuo, Mayo Ikeuchi, Shuichi Shimakawa, Kenji Shimizu, Seiji Mizuno, Masaya Kubota, Masao Adachi, Yoshiaki Saito, Kiyotaka Tomiwa, Kazuhiro Haginoya, Hironao Numabe, Yuko Kako, Ai Hayashi, Haruko Sakamoto, Yoko HirakiKoichi Minami, Kiyoshi Takemoto, Kyoko Watanabe, Kiyokuni Miura, Tomohiro Chiyonobu, Tomohiro Kumada, Katsumi Imai, Yoshihiro Maegaki, Satoru Nagata, Kenjiro Kosaki, Tatsuro Izumi, Toshiro Nagai, Toshiyuki Yamamoto

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features. Method: In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined. Results: We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region. Among them, blood samples were obtained from 50 patients (15 males and 35 females). The precise deletion regions were successfully genotyped. There were variable deletion patterns: pure terminal deletions in 38 patients (76%), including three cases of mosaicism; unbalanced translocations in seven (14%); and interstitial deletions in five (10%). Craniofacial/skeletal features, neurodevelopmental impairments, and cardiac anomalies were commonly observed in patients, with correlation to deletion sizes. Conclusion: The genotype-phenotype correlation analysis narrowed the region responsible for distinctive craniofacial features and intellectual disability into 1.8-2.1 and 1.8-2.2. Mb region, respectively. Patients with deletions larger than 6.2. Mb showed no ambulation, indicating that severe neurodevelopmental prognosis may be modified by haploinsufficiencies of KCNAB2 and CHD5, located at 6.2. Mb away from the telomere. Although the genotype-phenotype correlation for the cardiac abnormalities is unclear, PRDM16, PRKCZ, and RERE may be related to this complication. Our study also revealed that female patients who acquired ambulatory ability were likely to be at risk for obesity.

本文言語English
ページ(範囲)515-526
ページ数12
ジャーナルBrain and Development
37
5
DOI
出版ステータスPublished - 2015 5月 1

ASJC Scopus subject areas

  • 小児科学、周産期医学および子どもの健康
  • 発達神経科学
  • 臨床神経学

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