Novel karyotypes of partial monosomy 21 and partial monosomy 1 and underlying etiology

We report two novel karyotypes in the siblings of a Chinese family, 45,XY,der(1)t(1;21)(q44;q21)mat,-21 and 45,XX,der(1)t(1;21)(q44;q21)mat,-21. These karyotypes are the result of unbalanced inheritance of a maternal balanced reciprocal translocation 46,XX,t(1;21)(q44;q21). Both patients share a phenotype of intellectual disability, facial malformation, and infertility. The infertility is manifest by: azoospermia in the brother and recurrent spontaneous abortions (RSA) in the sister. Database search revealed recurrent copy number losses associated with these translocated regions. Here we propose that the partial deletion of the gene SMYD3 is responsible for both the intellectual disability in both patients, as well as the azoospermia in the male patient. Altogether, SMYD3 may be an important candidate gene for future research on male fertility.