Fine mapping of chromosome 17 translocation breakpoints > or = 900 Kb upstream of SOX9 in acampomelic campomelic dysplasia and a mild, familial skeletal dysplasia.
Previously, our group reported a five-generation family in which a balanced t(13;17) translocation is associated with a spectrum of skeletal abnormalities, including Robin sequence, hypoplastic scapulae, and a missing pair of ribs. Using polymerase chain reaction (PCR) with chromosome-specific markers to analyze DBA from somatic cell hybrids containing the derivative translocation chromosomes, we narrowed the breakpoint on each chromosome. Subsequent sequencing of PCR products spanning the breakpoints identified the breaks precisely. The chromosome 17 breakpoint maps approximately 932 kb upstream of the sex-determining region Y (SRY)-related high-mobility group box gene (SOX) within a noncoding transcript represented by two IMAGE cDNA clones. A growing number of reports have implicated chromosome 17 breakpoints at a distance of up to 1 Mb from SOX9 in some cases of campomelic dysplasia (CD). Although this multigeneration family has a disorder that shares some features with CD, their phenotype is significantly milder than any reported cases of (nonmosaic) CD. Therefore, this case may represent an etiologically distinct skeletal dysplasia or may be an extremely mild familial example of CD, caused by the most proximal translocation breakpoint from SOX9 reported to date. In addition, we have refined the breakpoint in a acampomelic CD case described elsewhere and have found that it lies approximately 900 kb upstream of SOX9.
Hill-Harfe
Katherine L
KL
Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, USA.
Kaplan
Lee
L
Stalker
Heather J
HJ
Zori
Roberto T
RT
Pop
Ramona
R
Scherer
Gerd
G
Wallace
Margaret R
MR
D001483:Base Sequence; D001848:Bone Diseases, Developmental / Q000235:genetics*; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors
Am J Med Genet. 1999 May 7;84(1):20-4
10213041
J Med Genet. 1993 Aug;30(8):683-6
8411055
Science. 2003 Oct 17;302(5644):413
14563999
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10649-54
9724758
Cytogenet Genome Res. 2003;101(3-4):185-98
14684982
Cytogenet Cell Genet. 1997;76(3-4):172-5
9186513
J Pediatr. 1976 Sep;89(3):512-3
956984
Nat Genet. 2001 Jul;28(3):216-7
11431689
Hum Mol Genet. 2003 Jul 15;12(14):1755-65
12837698
Clin Genet. 1980 Aug;18(2):137-41
7438495
Nature. 1991 May 9;351(6322):117-21
2030730
J Bone Miner Res. 1999 May;14(5):757-63
10320524
Nature. 1990 Nov 29;348(6300):452-4
2247151
Nature. 1990 Jul 19;346(6281):240-4
1695712
J Pediatr. 1973 Nov;83(5):841-3
4742578
Nucleic Acids Res. 1987 Oct 26;15(20):8125-48
3313277
J Med Genet. 2002 Aug;39(8):597-602
12161603
Hum Mol Genet. 2002 Jan 1;11(1):33-42
11772997
Am J Hum Genet. 1999 Jul;65(1):111-24
10364523
J Biol Chem. 1999 Aug 20;274(34):24023-30
10446171
J Med Genet. 1995 Jun;32(6):415-20
7666392
Hum Mol Genet. 1996 Jan;5(1):69-72
8789441
Hum Mol Genet. 1996 Sep;5(9):1229-35
8872461
Am J Med Genet A. 2005 Jan 1;132A(1):113; author reply 114-5
15578585
Hum Mol Genet. 1997 Jan;6(1):91-8
9002675
Nature. 1990 Nov 29;348(6300):448-50
2247149
J Med Genet. 1998 Jul;35(7):597-9
9678706
Am J Med Genet. 1995 Mar 13;56(1):31-4
7747782
Am J Hum Genet. 1995 Nov;57(5):1028-36
7485151
Hum Mol Genet. 2003 Jul 15;12(14):1725-35
12837695
Mol Cell Biol. 1997 Apr;17(4):2336-46
9121483
Nat Genet. 1997 Jun;16(2):174-8
9171829
Am J Med Genet. 1997 Dec 19;73(3):247-50
9415678
Cell. 1994 Dec 16;79(6):1111-20
8001137
Hum Genet. 1996 Feb;97(2):186-93
8566951
Hum Mol Genet. 2003 Jun 15;12(12):1439-47
12783851
Am J Med Genet. 1983 May;15(1):3-28
6344634
Prenat Diagn. 1985 Jan-Feb;5(1):1-8
3883340
J Med Genet. 1992 Apr;29(4):251-2
1583645
Am J Med Genet. 2001 Nov 1;103(4):339-41
11746016
J Biol Chem. 1998 Jun 12;273(24):14998-5006
9614107
J Med Genet. 2002 Sep;39(9):e50
12205120
Am J Hum Genet. 2005 Apr;76(4):652-62
15726498
Dev Biol. 1997 Mar 1;183(1):108-21
9119111
Indian J Dermatol Venereol Leprol. 2003 Nov-Dec;69(6):423-4
17642958
J Med Genet. 2004 Apr;41(4):e47
15060123
Nat Genet. 2000 Dec;26(4):490-4
11101852
Nature. 1994 Dec 8;372(6506):525-30
7990924
Hum Mol Genet. 2004 Jun 15;13(12):1213-8
15115764
Clin Genet. 1991 Jun;39(6):401-8
1677832
Pediatr Pathol Mol Med. 2003 Jan-Feb;22(1):37-46
12687888
Hum Mol Genet. 1996 Oct;5(10):1625-30
8894698
Am J Med Genet. 1999 Dec 3;87(4):349-53
10588843
Genomics. 2001 Nov;78(1-2):73-82
11707075