der(4)t(Y;4): Three-generation transmission and sperm meiotic segregation analysis

We present a family where five members (three males and two females) are carriers of der(4)t(Y;4)(q11.23;p16.3). The adult carriers are phenotypicaly normal and fertile; the boy shows macrocephaly, psychomotor retardation, and atypical autism. The FISH on cultured lymphocytes confirmed that the redundant Yq heterochromatin was attached to the 4p-subtelomeric region maintained on the der(4). Sperm FISH analysis performed in a normospermic der(4) carrier showed a significant distortion of the expected 1:1 ratio of the X- and Y-bearing spermatozoa in favor of the X chromosome and significant lack of Y,der(4)spermatozoa. The overall lack of Y spermatozoa was not balanced even by a relative excess of Y,4 sperm. The analysis of X, Y, 7, 8, 18, and 21 sperm disomy and diploidy did not indicate any interchromosomal effect. The chromosome 4 disomy was significantly increased but still very low to be of considerable reproductive significance. The neurodevelomental phenotype of the boy was probably caused by a gene mutation. The coincidental occurrence of such chromosomal aberration and boy's phenotype might lead to misinterpretation of the causal relationship between these findings. It is necessary to consider the results of chromosomal analysis and clinical records of relatives for provide genetic counseling in such families.