Dosage of Sex Chromosomal Genes in Blood Deposited on Filter Paper for Neonatal Screening of Sex Chromosome Aneuploidy

Genet Test Mol Biomarkers. 2016 Dec;20(12):786-790. doi: 10.1089/gtmb.2016.0101. Epub 2016 Oct 19.


Aims: In this study, we examined the doses of the stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY genes to establish a protocol for using peripheral blood samples deposited on filter paper for the screening of sex chromosome aneuploidy in neonates. We also measured correlations with karyotypes to assess this method as a neonatal screening strategy.

Materials and methods: This was an observational, descriptive, comparative blind study. Thirty-two healthy young adults (17 women, 15 men; age, ≥18 years), four patients with known sex chromosome aneuploidy (positive control group), and 1000 healthy newborns were included. Gene dosages were determined using quantitative real-time polymerase chain reaction (RT-PCR). Values with standard deviations (SDs) of three or more were considered abnormal.

Results: Men and women differed in the gene dosage of the SRY gene. Cases with Turner syndrome showed values below 3 SDs for SHOX and VAMP7 genes, and cases with Klinefelter syndrome showed values above 3 SDs for SHOX and VAMP7 genes. Two suspected cases of sex chromosome aneuploidy were diagnosed using our neonatal screening strategy; these cases were confirmed as Turner syndrome and 47,XYY syndrome by karyotyping.

Conclusions: Our data establish a basis for the determination of chromosomal sex and neonatal screening of sex chromosome aneuploidy using RT-PCR.

Keywords: aneuploidies; gene dosages; sex chromosome.

MeSH terms

  • Adolescent
  • Adult
  • Aneuploidy*
  • Child
  • Female
  • Gene Dosage
  • Homeodomain Proteins / blood
  • Homeodomain Proteins / genetics
  • Humans
  • Infant, Newborn
  • Karyotyping / methods
  • Klinefelter Syndrome / diagnosis
  • Klinefelter Syndrome / genetics
  • Male
  • Neonatal Screening / methods*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • R-SNARE Proteins / blood
  • R-SNARE Proteins / genetics
  • Sex Chromosome Aberrations*
  • Sex Chromosome Disorders
  • Sex Chromosomes*
  • Sex-Determining Region Y Protein / blood
  • Sex-Determining Region Y Protein / genetics
  • Short Stature Homeobox Protein
  • Turner Syndrome / diagnosis
  • Turner Syndrome / genetics
  • XYY Karyotype


  • Homeodomain Proteins
  • R-SNARE Proteins
  • SHOX protein, human
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • Short Stature Homeobox Protein
  • VAMP7 protein, human

Supplementary concepts

  • 47, XYY syndrome