Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature, primary amenorrhea, unilateral gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype.
We report on a 30-year-old woman with short stature, completely female external genitalia, primary amenorrhea, bilateral streak gonads, unilateral gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype. Variable levels of mosaicism were found in blood and cultivated fibroblasts from both the skin and ovaries, with the percentage of the 45,X lineage never exceeding 33%. Fluorescence in situ hybridization (FISH) was performed with alpha satellite centromere region probes of the X and Y chromosomes (DXZ1 and DXZ3) as well as with the unique-sequence, locus-specific, sex-determining region of the Y chromosome gene (SRY) and the DXZ1 probes. Each signal was noted for DXZ1 on the X chromosome and for the Y probes on the marker chromosome. Molecular investigations with a panel of PCR markers spread over the whole Y chromosome indicated a deletion breakpoint between sY 78 (interval 4) and sY 151 (interval 5F). No mutation of the high mobility group-box (HMG-box) of the SRY gene could be found following sequence analysis. The phenotype/genotype correlation demonstrates the broad phenotypic range of low-level 45,X mosaicism with the resultant short stature and external female phenotype, despite the presence of SRY in a high proportion of cells in various tissues.
Kotzot
Dieter
D
Institute for Human Genetics, University of Leipzig, Leipzig, Germany.
Dufke
Andreas
A
Tzschach
Andreas
A
Baeckert-Sifeddine
Iris-Tatjana
IT
Geppert
Martin
M
Holland
Heidrun
H
Florus
Jobst M
JM
Froster
Ursula G
UG
D000328:Adult; D000568:Amenorrhea / Q000235:genetics*; D001483:Base Sequence; D001827:Body Height / Q000235:genetics*; D002871:Chromosome Banding; D017931:DNA Primers; D005260:Female; D018238:Gonadoblastoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D009030:Mosaicism
D017931:DNA Primers