Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions

A novel microduplication in chromosome Xq28 was identified by comparative genomic hybridization in four cognitively impaired males who share behavioral abnormalities and characteristic facial features. These duplications occur as a result of unequal exchange between two homologous regions, int22h-1 and int22h-2, which, in addition to int22h-3, are also responsible for inversions disrupting the factor VIII gene in hemophilia A. A reciprocal Xq28 deletion was also detected in a girl and her mother, who had two spontaneous miscarriages. This report suggests that int22h-1/int22h-2-mediated Xq28 duplications are responsible for a novel X-linked intellectual disability syndrome, and that the reciprocal deletion may be lethal for males in utero. (By Ayman El-Hattab, M.D., F.A.A.P., )

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