INHERITED X-CHROMOSOME INVERTED TANDEM DUPLICATION IN A MALE TRACED TO A GRANDPARENTAL MITOTIC ERROR

Abstract

A male infant was referred for cytogenetic evaluation because of dysmorphic features and developmental delay. In both lymphocytes and skin fibroblasts, a modal number of 46 chromosomes was obtained with an obvious elongation of the long arm of the X chromosome (Xq+). Studies of seven members in 3 generations of this family showed that the proband''s mother, sister, and maternal grandmother were phenotypically normal carriers of this abnormal X chromosome. High resolution GTG- and RBG-banding defined the extra chromatin material as an inverted duplication of Xq21 .fwdarw. Xq24. This was supported by an approximate twofold increase in .alpha.-galactosidase A activity, localized to Xq21 .fwdarw. q24, observed in the proband''s lymphocytes and fibroblasts. BrdU-incorporation studies of the mother''s lymphocytes showed the abnormal X to be late replicating in all 100 cells studied and normal .alpha.-galactosidase A levels. Cytogenetic analysis of the maternal grandmother revealed cytogenetic mosaicism with one cell line containing the abnormal X (37%), and the other, a normal female karyotype (63%). This family is instructive since: (1) it represents only the second case of a dysmorphic male demonstrating a confirmed interstitial partial Xq duplication, and (2) the origin of this familial structural rearrangement has been traced to a grandparental mitotic error.