True hermaphroditism in a 46, XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): Molecular genetics and histological findings in a sporadic case

Journal Article · Mon Mar 01 04:00:00 EST 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6572826

Braun, A; Kammerer, S; Cleve, H; Loehrs, U; Schwarz, H P; Kuhnle, U ^[1]

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1. Univ. of Munich (Germany)

Recently, the gene for the determination of maleness has been identified in the sex-determining region on the short arm of the Y chromosome (SRY) between the Y-chromosomal pseudoautosomal boundary (PABY) and the ZFY gene locus. Experiments with transgenic mice confirmed that SRY is a part of the testis-determining factor (TDF). The authors describe a sporadic case of a patient with intersexual genitalia and the histological finding of ovotestes in the gonad, which resembles the mixed type of gonadal tissue without primordial follicle structures. The karyotype of the patient was 46,XY. By PCR amplification, they tested for the presence of SRY by using DNA obtained from histological gonadal slices. The SRY products of both DNA preparations were further analyzed by direct sequencing. All three parts of the sex-determining region of the Y chromosome could be amplified from leukocytic DNA. The patient's and the father's SRY sequences were identical with the published sequence. In the SRY PCR product of gonadal DNA, the wild-type and two point mutations were present in the patient's sequence, simulating a heterozygous state of a Y-chromosomal gene: one of the mutations was silent, while the other encoded for a nonconservative amino acid substitution from leucine to histidine. Subcloning procedures showed that the two point mutations always occurred together. The origin of the patient's intersexuality is a postzygotic mutation of the SRY occurring in part of the gonadal tissue. This event caused the loss of the testis-determining function in affected cells. 37 refs., 6 figs.

• OSTI ID: 6572826
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:3; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMPLIFICATION
BODY
CHROMOSOMES
DETECTION
DNA
DNA SEQUENCING
FEMALE GENITALS
GENE MUTATIONS
GENES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
HUMAN Y CHROMOSOME
MALE GENITALS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
SEX
STRUCTURAL CHEMICAL ANALYSIS
Y CHROMOSOME