1/3. Birth of healthy female twins after preimplantation genetic diagnosis of cystic fibrosis combined with gender determination.Two healthy sisters with a familial history of mental retardation were referred to our centre for preimplantation genetic diagnosis (PGD). Their two brothers showed severe mental retardation. The molecular basis for their disorder could not be identified, but one of the sisters and the mother presented a highly skewed pattern of X-inactivation reinforcing the likelihood of an X-linked mode of inheritance. Both sisters requested PGD to avoid the abortion of potentially affected male fetuses. PGD for sex by fluorescent in-situ hybridization was carried out for the first sister and resulted in the birth of a female child. The second sister and her partner, whose niece had cystic fibrosis (CF), were tested for CF mutations, and were both found to be deltaF508 heterozygous. We developed an efficient single cell PCR protocol for the simultaneous amplification of the CF (deltadeltaF508) locus as well as the X-linked amelogenin gene and its highly homologous pseudogene on the y chromosome. Two PGD cycles were carried out to screen against male and deltaF508 homozygous deleted embryos. In each case several embryos could be selected for transfer and the second cycle resulted in a twin pregnancy followed by the birth of two healthy female infants.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/3. Mental retardation and early onset of weakness in a girl with a dystrophinopathy and a large Xp21-23 deletion.A 2-year-old girl presented with severe global developmental delay weakness, and an elevated serum creatine kinase level. Her muscle biopsy was consistent with an active dystrophy with absence of dystrophin in about half of the muscle fibers. Fluorescent in situ hybridization analysis showed her karyotype to be 46, X, delX p23.1-p21.1. This large deletion includes the dystrophin gene as well as the region involved in X-linked mental retardation. The genetic mechanism for the manifestation of both diseases is likely non-random inactivation of the x chromosome. To our knowledge, the combination of this dystrophinopathy in association with severe mental retardation has not been described in a girl.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/3. dissection of an inverted X(p21.3q27.1) chromosome associated with mental retardation.In a 6 year old boy referred for mental retardation, fragile x syndrome was ruled out by cytogenetic and molecular analyses. Cytogenetic investigations revealed an inverted x chromosome (p21.3q27.1). A similar chromosomal rearrangement was detected in his mildly mentally retarded mother. fluorescence in situ hybridization (FISH), using a panel of ordered YAC clones, allowed the identification of YACs spanning both the Xp21.3 and Xq27.1 breakpoints, where many non-specific mental retardation loci have been reported so far. Further investigations by FISH showed that the IL1RAPL1 gene at Xp21.3 was disrupted by the X chromosome inversion and therefore its inactivation may be related to the mental retardation observed in our patients.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |