title: Establishing SON in 21q22.11 as a cause a new syndromic form of intellectual disability: Possible contribution to Braddock-Carey syndrome phenotype.
abstract: A recent study of exome analyses in 109 patients with undiagnosed diseases included a 5-year-old girl with intellectual disability and multiple congenital anomalies, who had an apparently de novo frameshift mutation in SON. However, the combination of the truncating mutation in SON and the phenotype has not been reproduced until date, and it remains unclear if this combination represents a distinctive disease entity. Here we report an additional male with intellectual disability, congenital heart disease, distinctive facial features with curly hair and protruding ears, and long slender extremities, and hyperextensible joints. Exome analysis showed that he had the same de novo frameshift mutation in SON in a heterozygous state. Along with the first and original description of the apparently de novo truncating mutation in SON mentioned above, we have established that haploinsufficiency of SON causes a new recognizable syndrome of intellectual disability. SON is located within 21q22.11, a critical region for Braddock-Carey syndrome, which is characterized by congenital thrombocytopenia, intellectual disability, micrognathia, and a distinctive facies. Therefore, we suggest that the intellectual disability observed in Braddock-Carey syndrome could be accounted for by haploinsufficiency of SON. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.|Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Department of Child Neurology, Toyota Municipal Child Development Center, Aichi, Japan.
authors.forename: Kiyokuni
authors.initials: K
authors.lastname: Miura
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Pediatrics, Central Hospital, Aichi Human Service Center, Aichi, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan. kkosaki@keio.jp.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
mesh_terms: D000293:Adolescent; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D019066:Facies; D016368:Frameshift Mutation; D006130:Growth Disorders / Q000175:diagnosis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D010855:Pierre Robin Syndrome / Q000175:diagnosis; D013577:Syndrome; D013921:Thrombocytopenia / Q000151:congenital / Q000175:diagnosis
chemical_list: D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C088203:SON protein, human
keywords: 21q22; Braddock-Carey syndrome; SON; intellectual disability; thrombocytopenia