Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome.
Coffin-Siris syndrome is a rare congenital malformation and intellectual disability syndrome. Mutations in at least seven genes have been identified. Here, we performed copy number analysis in 37 patients with features of CSS in whom no causative mutations were identified by exome sequencing. We identified a patient with a 9p24.3-p22.2 duplication and another patient with the chromosome der(6)t(6;9)(p25;p21)mat. Both patients share a duplicated 15.8-Mb region containing 46 protein coding genes, including SMARCA2. Dominant negative effects of SMARCA2 mutations may contribute to Nicolaides-Baraitser syndrome. We conclude that their features better resemble Coffin-Siris syndrome, rather than Nicolaides-Baraitser syndrome and that these features likely arise from SMARCA2 over-dosage. Pure 9p duplications (not caused by unbalanced translocations) are rare. Copy number analysis in patients with features that overlap with Coffin-Siris syndrome is recommended to further determine their genetic aspects. © 2016 Wiley Periodicals, Inc.
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. nmiyake@yokohama-cu.ac.jp.
Noriko
N
Miyake
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Ghada
G
Abdel-Salam
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Takanori
T
Yamagata
Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Maha M
MM
Eid
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Hitoshi
H
Osaka
Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Nobuhiko
N
Okamoto
Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Amal M
AM
Mohamed
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Takahiro
T
Ikeda
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Hanan H
HH
Afifi
Centre de Génétique Humaine, Université de Franche-Comté, CHU Besançon, Besançon, France.
Juliette
J
Piard
Centre de Génétique Humaine, Université de Franche-Comté, CHU Besançon, Besançon, France.
Lionel
L
van Maldergem
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takeshi
T
Mizuguchi
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Satoko
S
Miyatake
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yoshinori
Y
Tsurusaki
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. naomat@yokohama-cu.ac.jp.
Naomichi
N
Matsumoto
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000483:Alleles; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D059472:Exome; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D020440:Gene Duplication; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008844:Micrognathism / Q000175:diagnosis* / Q000235:genetics*; D009333:Neck / Q000002:abnormalities*; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
C084011:SMARCA2 protein, human; D014157:Transcription Factors
9p duplication; Coffin-Siris syndrome; Nicolaides-Baraitser syndrome; SMARCA2; copy number change