Chromosomal rearrangements in Xq and premature ovarian failure: mapping of 25 new cases and review of the literature.
BACKGROUND
Chromosomal rearrangements in Xq are frequently associated with premature ovarian failure (POF) and have defined a POF 'critical region'. Search for genes responsible for the disorder has been elusive.


METHODS
We report mapping of novel breakpoints of X;autosome-balanced translocations and interstitial deletions and a review of published X chromosome rearrangements.


RESULTS
All the novel POF-associated rearrangements were mapped outside and often very distant from genes. The majority mapped to a gene-poor region in Xq21. In the same region, deletions were reported in women who apparently did not have problems conceiving. Expression analysis of genes flanking breakpoints clustered in a 2-Mb region of Xq21 failed to demonstrate ovary-specific genes.


CONCLUSIONS
Our results excluded most of the possible explanations for the POF phenotype and suggested that POF should be ascribed to a position effect of the breakpoints on flanking genes. We also showed that while the X breakpoint may affect X-linked genes in the distal part of Xq, from Xq23 to Xq28, interruption of the critical region in Xq21 could be explained by a position effect of the Xq critical region on genes flanking the autosomal breakpoints.
Rizzolio
Flavio
F
DIBIT, San Raffaele Scientific Institute, Milano, Italy.
Bione
Silvia
S
Sala
Cinzia
C
Goegan
Mara
M
Gentile
Mattia
M
Gregato
Giuliana
G
Rossi
Elena
E
Pramparo
Tiziano
T
Zuffardi
Orsetta
O
Toniolo
Daniela
D
D000328:Adult; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D008875:Middle Aged; D008957:Models, Genetic; D010053:Ovary / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D014178:Translocation, Genetic