Inherited X-chromosome inverted tandem duplication in a male traced to a grandparental mitotic error.
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----Xq24. This was supported by an approximate twofold increase in alpha-galactosidase A activity, localized to Xq21----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.
Schwartz
S
S
Schwartz
M F
MF
Panny
S R
SR
Peterson
C J
CJ
Waters
E
E
Cohen
M M
MM
D000328:Adult; D007446:Chromosome Inversion; D005145:Face / Q000002:abnormalities; D005260:Female; D005696:Galactosidases / Q000235:genetics; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008938:Mitosis; D010375:Pedigree; D012729:Sex Chromosome Aberrations / Q000235:genetics; D014960:X Chromosome
D005819:Genetic Markers; D005696:Galactosidases