Paternal origin of der(X)t(X;6) in a girl with trisomy 6p and unbalanced t(6;10) mosaicism in her mother

Abstract

We present a case of trisomy for the whole short arm of chromosome 6 in a 3-year-old girl with moderate mental retardation, mild facial dysmorphism, short stature, failure to thrive, and no abnormalities of the visceral organs. Cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed a 46, X, der(X)t(X;6)(q22; p11.1) karyotype. The derived X was late replicating with variable spreading of X chromosome inactivation onto the translocated 6p. A normal karyotype was observed in the father, while the mother presented 46,XX/46,XX, der(10)t(6;10)(p11;p11). The mother is a mosaic with unbalanced t(6;10) in 4.7% of cells. To the best of our knowledge, this unusual mosaicism has not yet been reported. In this family the short arm of chromosome 6 was involved in an unbalanced rearrangement with chromosome X in the proband and with chromosome 10 in the mother. In order to study the mechanism of the formation of t(X;6) in the girl we performed DNA polymorphism analysis. These investigations revealed that chromosomes X and 6 involved in the rearrangement are of paternal origin. Our patient exhibits only discrete facial features characteristic of partial trisomy 6p. We suggest that mild phenotypic expression be probably due to X chromosome inactivation spreading onto the translocated 6p. This report show that combined cytogenetic, FISH, and molecular analysis of chromosomal aberrations are necessary for the understanding of the mechanism of formation, parental origin, and genetic counseling.