Paternal somatic and germ-line mosaicism for a sex-determining region on Y (SRY) missense mutation leading to recurrent 46,XY sex reversal.
OBJECTIVE
To determine the etiology for recurrent 46,XY sex reversal in a family with two Swyer siblings.


METHODS
Deoxyribonucleic acid (DNA) from peripheral lymphocytes and sperm were analyzed for duplication of the dosage sensitive sex locus (DSS) and for mutations in sex-determining region on Y (SRY).


METHODS
An academic teaching hospital.


METHODS
A family consisting of mother, father, and five phenotypic daughters, of which two were 46,XY sex-reversed females.


METHODS
Deoxyribonucleic acid (DNA) extraction, polymerase chain reaction (PCR), Southern blotting, dosage densitometry, single-strand conformation polymorphism (SSCP), and sequencing.


METHODS
Comparison of control and subject DNA.


RESULTS
Deoxyribonucleic acid (DNA) analysis of SRY in genomic DNA from the 46,XY sex-reversed siblings revealed identical missense mutations (T-->G) in both sisters. Analysis of the SRY gene in paternal lymphocyte and sperm DNA revealed mosaicism for wild and mutant (T-->G) SRY sequences. SRY analysis of sperm DNA also demonstrated the same mosaicism for the T-->G missense mutation.


CONCLUSIONS
A postembryonic SRY mutation gave rise to paternal mosaicism for two distinct cell populations (SRY+/SRY-). The presence of a wild type SRY in the somatic cell line may account for a normal pattern of male sexual differentiation, whereas the presence of a mutated SRY in the germ line resulted in two 46,XY sex-reversed offspring. These results confirm a proposed mechanism for the condition of recurrent 46,XY sex-reversed females.
Hines
R S
RS
Medical College of Georgia, Augusta, USA.
Tho
S P
SP
Zhang
Y Y
YY
Plouffe
L
L
Hansen
K A
KA
Khan
I
I
McDonough
P G
PG
D000293:Adolescent; D015139:Blotting, Southern; D002648:Child; D004247:DNA / Q000032:analysis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015894:Genome, Human; D006061:Gonadal Dysgenesis, 46,XY / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013094:Spermatozoa / Q000737:chemistry; D014998:Y Chromosome / Q000235:genetics*
D017931:DNA Primers; D004247:DNA