Genetic test may provide simple method to diagnose Klinefelter's

Methylation-specific polymerase chain reaction (M-PCR) is a sensitive, specific, fast, and relatively inexpensive method of diagnosing Klinefelter's syndrome, according to data presented here by Peter N. Schlegel, MD, and colleagues from Cornell University, New York.

M-PCR may serve as an adjunct to karyotype and Y chromosome microdeletion assay, both of which are widely recommended forms of screening for men with low sperm production.

"This form of testing may advance our ability to detect genetic conditions in a more specific way than our current genetic testing methods," said Dr. Schlegel, professor and chairman of urology at Cornell. "A gene-specific test should be more specific than a gross karyotype test, capable of detecting copy numbers of a gene rather than the presence or absence of an entire chromosome."

The researchers used M-PCR with primers for familial mental retardation 1 (FMR1) and X-chromosome inactivation transcript (CIST) genes to detect the presence of X-chromosome disomy in men. They extracted DNA from blood samples from 17 fertile males; 12 females; seven males with 47, XXY/46, XY mosaicism; and 28 males with 47, XXY karyotype.

They then performed M-PCR with methylation-specific primers, comparing results with known karyotype. The team also assessed X-chromosome inactivation patterns by measuring the net intensity of methylated and unmethylated XIST amplicons after gel electrophoresis.

They found that the methylation pattern of FMR1 and XIST genes in Klinefelter's syndrome patients is the same as in females with one copy of the XIST gene methylated (inactive) and the other unmethylated (active).