TY - JOUR
T1 - Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications
AU - Shimada, Shino
AU - Shimojima, Keiko
AU - Okamoto, Nobuhiko
AU - Sangu, Noriko
AU - Hirasawa, Kyoko
AU - Matsuo, Mari
AU - Ikeuchi, Mayo
AU - Shimakawa, Shuichi
AU - Shimizu, Kenji
AU - Mizuno, Seiji
AU - Kubota, Masaya
AU - Adachi, Masao
AU - Saito, Yoshiaki
AU - Tomiwa, Kiyotaka
AU - Haginoya, Kazuhiro
AU - Numabe, Hironao
AU - Kako, Yuko
AU - Hayashi, Ai
AU - Sakamoto, Haruko
AU - Hiraki, Yoko
AU - Minami, Koichi
AU - Takemoto, Kiyoshi
AU - Watanabe, Kyoko
AU - Miura, Kiyokuni
AU - Chiyonobu, Tomohiro
AU - Kumada, Tomohiro
AU - Imai, Katsumi
AU - Maegaki, Yoshihiro
AU - Nagata, Satoru
AU - Kosaki, Kenjiro
AU - Izumi, Tatsuro
AU - Nagai, Toshiro
AU - Yamamoto, Toshiyuki
N1 - Funding Information:
We would like to express our gratitude to the patients and their families for their cooperation. We also thank the Japanese Society of Child Neurology and the Japan Society of Pediatric Genetics for their supports. This work was supported by a Grant-in-Aid for Scientific Research from Health Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare , Japan.
Publisher Copyright:
© 2014 The Japanese Society of Child Neurology.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - 1p36 deletion syndrome
KW - Ambulation
KW - Chromosomal deletion
KW - Distinctive features
KW - Epilepsy
KW - Genotype-phenotype correlation
KW - Intellectual disability
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U2 - 10.1016/j.braindev.2014.08.002
DO - 10.1016/j.braindev.2014.08.002
M3 - Article
C2 - 25172301
AN - SCOPUS:84925272911
VL - 37
SP - 515
EP - 526
JO - Brain and Development
JF - Brain and Development
SN - 0387-7604
IS - 5
ER -