title: Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hirasawa
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics and Child Neurology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Mayo
authors.initials: M
authors.lastname: Ikeuchi
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shimakawa
authors.affiliation: Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, Central Hospital, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Kakogawa Hospital Organization, Kakogawa West-City Hospital, Kakogawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, Medical Center for Children, Osaka City General Hospital, Osaka, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Tomiwa
authors.affiliation: Department of Pediatric Neurology, Takuto Rehabilitation Center for Children, Sendai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haginoya
authors.affiliation: Department of Genetic Counseling, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Hironao
authors.initials: H
authors.lastname: Numabe
authors.affiliation: Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kako
authors.affiliation: Department of Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Pediatrics, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Hiroshima Municipal Center for Child Health and Development, Hiroshima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hiraki
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Minami
authors.affiliation: Osaka Developmental Rehabilitation Center, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takemoto
authors.affiliation: Department of Pediatrics, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Developmental Disability Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kiyokuni
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Chiyonobu
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Moriyama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kumada
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Division of Child Neurology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maegaki
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagata
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.affiliation: Department of Pediatrics and Child Neurology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D055815:Young Adult
keywords: 1p36 deletion syndrome; Ambulation; Chromosomal deletion; Distinctive features; Epilepsy; Genotype–phenotype correlation; Intellectual disability