Lisa H. Gibson

Familial dup(5)(q15q21) associated with normal and abnormal phenotypes

We studied a familial dup(5q) present in a phenotypically normal father and his monozygotic twin daughters with different abnormal phenotypes. High-resolution chromosome analysis suggested that the duplicated segment was of region q15-21, which seems to be the smallest dup(5q) reported thus far. This dup(5q) was confirmed by fluorescence in situ hybridization with a chromosome 5 painting library and 5q cosmid clones. The presence of the dup(5q) in a normal father suggested that the duplication itself may be harmless. The anomalies in the twins may be due to processes other than this chromosome change.

A complex chromosome rearrangement with at least five breakpoints studied by fluorescence in situ hybridization

A newborn infant with multiple congenital anomalies was diagnosed with an unbalanced translocation of chromosomes 1 and 5. Studies of parental chromosomes revealed a complex rearrangement in the patients mother involving the exchange of terminal long arms between chromosomes 1 and 5 and the insertion of an interstitial segment from the same chromosome 5q into chromosome 2q by high-resolution G-banding. Further study of the mothers chromosomes by fluorescent in situ hybridization (FISH) detected an additional insertion between the rearranged chromosomes 2 and 5, which was not revealed by G-banding. This led to the identification of a complex translocation-insertion between 3 chromosomes with at least 5 breaks [t(1;5;2)(1pter--> 1q42.3::5q23.2-->5qter;5pter-->5q21.2:: 2q33--> 2q35::1q42.3-->1qter;2pter-->2q33::5q21 .2--> 5q23.2::2q35-->2qter)] and illustrates the value of FISH as an adjunct to standard cytogenetics, particularly in cases of complex rearrangements.

Cytogenetic and molecular studies of a familial paracentric inversion of 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 ambiguous genitalia. FISH analyses with Y chromosome YACs demonstrated that the inversion breakpoints of the patients and the fathers Ys appear to be the same and lie within interval 5B of the Y chromosome. PCR and sequence analysis indicated that our patient carries a normal SRY gene. For an additional comparison of the patients inv(Y) with the father, two other Y chromosome sequences were examined. Molecular studies of this familial inverted Y chromosome showed no differences in the ZFY and TSPY genes between the father and the patient suggesting that the short arm of our patients inv(Y) is identical to that of the patients father. Southern analysis using a probe of the DAX-1 gene indicated that a single copy of DSS (dosage sensitive sex reversal) locus was present in the patient. Our results suggest that the abnormal sexual development 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.

A de novo satellited short arm of the Y chromosome possibly resulting from an unstable translocation

A satellited long arm of the Y chromosome (Yqs) is considered a normal variation, whereas the presence of a satellite on the short arm of the Y (Yps) has never been described in the literature. A Yps chromosome could be clinically significant if the translocation resulting in Yps has relocated the testis-determining gene, SRY, to another chromosome. A carrier of such a translocation would therefore be at increased risk for having XX male and XY female offspring. Here we describe the first reported case of de novo Yps present in a phenotypically normal male. This Yps chromosome was positive for C-banding and nucleolus organizer region (NOR) staining and showed a hybridization signal for the β-satellite sequence. Fluorescence in situ hybridization (FISH) analysis indicated that SRY was retained on the Yps and the translocation breakpoint on Yps was distal to the pseudoautosomal region. At prenatal diagnosis, a normal appearing Y chromosome was found in his son, and thus the satellite on Yps was lost during meiotic Xp-Yp pairing. This Yps chromosome was likely the product of an “unstable” translocation.