Fine Mapping of Chromosome 17 Translocation Breakpoints ⩾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 marke...

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Bibliographic Details
Published in:American journal of human genetics 2005-04, Vol.76 (4), p.663-671
Main Authors: Hill-Harfe, Katherine L., Kaplan, Lee, Stalker, Heather J., Zori, Roberto T., Pop, Ramona, Scherer, Gerd, Wallace, Margaret R.
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Bone Diseases, Developmental - genetics
Chromosome aberrations
Chromosome Breakage
Chromosome Mapping
Chromosomes
Chromosomes, Human, Pair 17
Deoxyribonucleic acid
Diseases of the osteoarticular system
DNA
General aspects. Genetic counseling
Genomics
High Mobility Group Proteins - genetics
Humans
Male
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical genetics
Medical sciences
Molecular Sequence Data
Skeletal system
SOX9 Transcription Factor
Transcription Factors - genetics
Translocation, Genetic
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Summary: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 DNA 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 ∼932 kb upstream of the sex-determining region Y ( SRY)–related high-mobility group b ox gene ( SOX9) 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 an acampomelic CD case described elsewhere and have found that it lies ∼900 kb upstream of SOX9.
ISSN:0002-9297
1537-6605
DOI:10.1086/429254