Detection of Turner Syndrome Using High-Throughput Quantitative Genotyping

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 6; pp. 3419 - 3422
• Main Authors: Meng, Haiying, Hager, Karl, Rivkees, Scott A., Gruen, Jeffrey R.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-06-2005
• Subjects: Biological and medical sciences; Chromosomes, Human, X - genetics; Chromosomes, Human, Y - genetics; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Genotype; Humans; Karyotyping; Male; Medical sciences; Noonan Syndrome - genetics; Turner Syndrome - genetics; Vertebrates: endocrinology; Chromosomal aberration; Dysgenesia; Malformation; Gonad; Genital system; Genotype; Sexual differentiation disorder; Diagnosis; Turner syndrome; Endocrinology; Female genital diseases; Quantitative analysis
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-0544

Context: Turner syndrome (TS) is the most common genetic problem affecting women and occurs when an X chromosome is completely deleted, portions of an X chromosome are deleted, or chromosomal mosaicism occurs. Girls with TS may also have occult Y chromosome sequences. Whereas some girls with TS are identified in infancy or early childhood, many girls with TS are not detected until after 10 yr of age, resulting in delayed evaluation and treatment.
Objective: To prevent the delayed recognition and treatment of TS, a quantitative method of genotyping that can be performed as part of newborn screening is needed.
Design: To screen for sex chromosome abnormalities, we assembled a panel of informative single nucleotide polymorphism (SNP) markers that span the X chromosome from the dbSNP database. Pyrosequencing assays suitable for quantitative assessment of signal strength from single nucleotides were designed and used to genotype 46,XX; 46,XY; 45,X; and TS mosaics, examining zygosity and signal strength for individual alleles. Pyrosequencing assays were also designed for the detection of Y chromosome material.
Results: With just four informative SNP markers for the X chromosome, all TS girls with 45,X, partial X chromosome deletions, or mosaicism were identified with 100% sensitivity. In mosaic individuals, Y chromosomal material was detected with 100% sensitivity.
Conclusion: These results suggest that inexpensive high-throughput screening is possible for TS and other sex chromosome disorders using quantitative genotyping approaches.