Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.
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.
Nakabayashi
Kazuhiko
K
Department of Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
Fernandez
Bridget A
BA
Teshima
Ikuko
I
Shuman
Cheryl
C
Proud
Virginia K
VK
Curry
Cynthia J
CJ
Chitayat
David
D
Grebe
Theresa
T
Ming
Jeffrey
J
Oshimura
Mitsuo
M
Meguro
Makiko
M
Mitsuya
Kohzoh
K
Deb-Rinker
Paromita
P
Herbrick
Jo-Anne
JA
Weksberg
Rosanna
R
Scherer
Stephen W
SW
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