CYTOGENETIC AND MOLECULAR STUDIES OF A FAMILIAL PARACENTRIC INVERSIONOF Y-CHROMOSOME PRESENT IN A PATIENT WITH AMBIGUOUS GENITALIA

Here we describe the first reported case of a patient with a familial paracentric inversion in the long arm of the Y chromosome and ambiguou s genitalia. FISH analyses with Y chromosome YACs demonstrated that th e inversion breakpoints of the patients and the father's Ys appear to be the same and lie within interval 5B of the Y chromosome, PCR and se quence analysis indicated that our patient carries a normal SRY gene, For an additional comparison of the patient's inv(Y) with the father, two other Y chromosome sequences were examined. Molecular studies of t his familial inverted Y chromosome showed no differences in the ZFY an d TSPY genes between the father and the patient suggesting that the sh ort arm of our patient's inv(Y) is identical to that of the patient's father, Southern analysis using a probe of the DAX-1 gene indicated th at a single copy of DSS (dosage sensitive sex reversal) locus was pres ent in the patient, Our results suggest that the abnormal sexual devel opment in our patient is likely attributable to (an)other mechanism(s) than mutation in the SRY gene and dosage alteration of the DAX-1 gene . (C) 1997 Wiley-Liss, Inc.