title: Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.
abstract: Russell-Silver syndrome (RSS) is a form of congenital short stature characterized by severe growth retardation and variable dysmorphic features. In some RSS individuals, alterations in imprinted genes may be involved because approximately 7% of sporadic patients have been observed to have maternal uniparental disomy (mUPD) of chromosome 7. RSS patients with structural abnormalities of chromosome 7 have also been described. In these individuals the chromosome rearrangement could disrupt the balance of imprinted genes, contribute to a recessive form of RSS, or lead to haploinsufficiency of a crucial developmental gene product. Because the mechanism and molecular defects on chromosome 7 causing RSS are still unknown, we tested our collection of 77 RSS families for mUPD7 and were able to identify three new cases. We also characterized two RSS patients with de novo cytogenetic abnormalities involving the short arm of chromosome 7. One had a partial duplication [46, XX, dup(7)(p12 p14)] and the second contained a paracentric inversion [46, XY, inv(7)(p14 p21)]. Fluorescence in situ hybridization (FISH) mapping revealed that the breakpoints on 7p14 were localized to the same novel gene, C7orf10, which encompasses >700 kb of DNA. We also identified other transcription units from this immediate region, but all seem to be biallelically expressed when using a somatic cell hybrid assay.
authors.affiliation: Department of Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.forename: Ikuko
authors.initials: I
authors.lastname: Teshima
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shuman
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Proud
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Curry
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Theresa
authors.initials: T
authors.lastname: Grebe
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ming
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.forename: Makiko
authors.initials: M
authors.lastname: Meguro
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Mitsuya
authors.forename: Paromita
authors.initials: P
authors.lastname: Deb-Rinker
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Herbrick
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001827:Body Height / Q000235:genetics; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D020732:Cytogenetic Analysis; D019066:Facies; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013577:Syndrome