Report of fertility in a woman with a predominantly 46,XY karyotype in a family with multiple disorders of sexual development.
BACKGROUND
We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X).


METHODS
A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis.


RESULTS
Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage.


CONCLUSIONS
The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.
Dumic
Miroslav
M
Department of Pediatric Endocrinology and Diabetes, University Hospital Rebro, Zagreb, Croatia 41000.
Lin-Su
Karen
K
Leibel
Natasha I
NI
Ciglar
Srecko
S
Vinci
Giovanna
G
Lasan
Ruzica
R
Nimkarn
Saroj
S
Wilson
Jean D
JD
McElreavey
Ken
K
New
Maria I
MI
D000293:Adolescent; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics* / Q000502:physiology; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D004247:DNA