Does chromosome 22 have anything to do with sex determination: further studies on a 46,XX,22q11.2 del male.

Several years ago, we presented a patient with true hermaphroditism and partial duplication of chromosome 22 and no evidence of SRY (Aleck et al. [1999: Am J Med Genet 85:2-4]). Recently a 46,XX male with velocardiofacial syndrome and a deletion of 22q11.2 and no evidence of Y chromosomal loci in blood DNA was reported (Phelan et al. [2003: Am J Med Genet 116A:77-79]). We have restudied this patient as he enters puberty. Because chromosomal deletions sometimes involve micro rearrangements of nearby material, we have extensively studied this individual's chromosome 22 looking for evidence of any gene duplication. We studied a number of variable number tandem repeat (VNTR) loci along chromosome 22 in the patient and both parents. Normal Mendelian inheritance of the VNTRs was found. We then used quantitative multiplex PCR of short fluorescent fragments (QMPSF) to delineate the 22q11.2 deletion in this patient (Jacquet et al. [2002: Hum Molec Genet 11:2243-2249]) and found a pattern of deletion typical of the velocardiofacial DiGeorge syndrome. Finally, the patient's DNA has been analyzed using a full coverage human chromosome 22 genomic microarray (array comparative genomic hybridization [CGH]) for evidence of rearrangements outside the classical velocardiofacial DiGeorge associated deletion (Buckley et al. [2002: Hum Molec Genet 11:3221-3229]). The array-CGH profile of this patient confirms the deletion encompassing the typically deleted region associated with the velocardiofacial DiGeorge syndrome and provides no support for additional gene copy number aberrations on 22q. Thus, there is no evidence of any chromosome 22 trisomic material. In this case, the rare events of sex reversal and 22q11.2 deletion may have occurred together by chance. Copyright 2003 Wiley-Liss, Inc.