title: Silver-Russell syndrome without body asymmetry in three patients with duplications of maternally derived chromosome 11p15 involving CDKN1C.
abstract: We report duplications of maternally derived chromosome 11p15 involving CDKN1C encoding a negative regulator for cell proliferation in three Japanese patients (cases 1 and 2 from family A and case 3 from family B) with Silver-Russell syndrome (SRS) phenotype lacking hemihypotrophy. Chromosome analysis showed 46,XX,der(16)t(11;16)(p15.3;q24.3)mat in case 1, 46,XY,der(16)t(11;16)(p15.3;q24.3)mat in case 2 and a de novo 46,XX,der(17)t(11;17)(p15.4;q25.3) in case 3. Genomewide oligonucleotide-based array comparative genomic hybridization, microsatellite analysis, pyrosequencing-based methylation analysis and direct sequence analysis revealed the presence of maternally derived extra copies of the distal chromosome 11p involving the wild-type CDKN1C (a ~7.98 Mb region in cases 1 and 2 and a ~4.43 Mb region in case 3). The results, in conjunction with the previous findings in patients with similar duplications encompassing CDKN1C and in those with intragenic mutations of CDKN1C, imply that duplications of CDKN1C, as well as relatively mild gain-of-function mutations of CDKN1C lead to SRS subtype that usually lack hemihypotrophy.
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kato
authors.affiliation: Department of Human Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.affiliation: Department of Pediatrics, Niigata University School of Medicine, Niigata, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagasaki
authors.affiliation: Department of Pediatrics, Saitama Medical University, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kagami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D058674:Chromosome Duplication; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D019175:DNA Methylation; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D006801:Humans; D059785:Karyotype; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA; D056730:Silver-Russell Syndrome / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57