Application of X chromosome inactivation analysis in prenatal diagnosis for family members affected with Xq28 duplication

Abstract

Objective To discuss the phenotype-genotype relations of Xq28 duplication syndrome between different members in a family and reveal the application value of X chromosome inactivation (XCI) analysis in X-linked disorders in prenatal diagnosis. Methods Chromosomal microarray analysis (CMA) was performed on the fetus and multiple ligation-dependent probe amplification (MLPA) was investigated for the affected boy and their mother to assess the copy number changes. XCI analysis was also performed on DNAs of the mother and her female fetus. We then analyzed genotype-phenotype relation based on these results and previous reports. Results The fetus was female and carried a 631 kb duplication on Xq28 (arr[hg19] Xq28(152, 993, 329~153, 624, 605)x3). The boy also had a duplication at this region, which quite likely was the cause of his mental retardation. This duplication was inherited from their unaffected mother. X-chromosome inactivation identifies the carrier mother with a skewed XCI that duplication-bearing X chromosome being preferentially inactivated. Her daughter possessed the same abnormal X chromosome with XCI ratio of 17/83. Conclusion Duplication of Xq28 might be associated with severe phenotype in both male and female. When prenatal genetic result reveals a female baby with an X-linked disease, XCI analysis and detailed anatomic scanning might be helpful in further prognosis of the baby. Key words: X-linked disease; Xq28 duplication syndrome; Molecular diagnosis; X chromosome inactivation; Genotype-phenotype analysis