FISH approach to determine cat eye syndrome chromosome breakpoints of a patient with cat eye syndrome type II.

We report a 19-year-old man with craniofacial dysmorphic features, anorectal malformations, eye colobomas, orthopaedic anomalies, and mild neurodevelopmental delay. Cat eye syndrome (CES) was suspected, and confirmed by cytogenetic analysis which showed the presence of a supernumerary bisatellited chromosome, identified by fluorescence in situ hybridization (FISH) as invdup(22). The marker was further analyzed with six BAC clones located at the 22q11.1 and 22q11.2 regions; this analysis allowed correct assignment at low copy repeat 4 on chromosome 22 (LCR22-4) of the two breakpoints, confirming the presence of a CES chromosome type II. The patient's phenotype is considered in the light of the cytogenetic, and FISH investigations results and other patients reported in literature. Molecular definition of the breakpoints at the LCR22-4 copy confirms the role of different chromosome 22-specific LCRs in CES chromosomes generation, as well as in other chromosome 22 germ line rearrangements. Our report confirms that, unlike other conditions, i.e. the invdup(15) bisatellited dicentric marker, the CES phenotype does not appear to correlate with the size of the marker chromosome. Additional cases are necessary to be able to draw more specific genotype-phenotype correlations and to determine the outcome of patients with CES, especially when this rare condition is diagnosed in prenatal age.

Identification of two SNPs in the 5' flanking region of the ACP1 gene and evaluation of disequilibrium among polymorphic sites.

We have studied the 5' flanking region of the ACP1 gene looking for new polymorphisms. Two SNPs, DdeI and FokI restricted, have been found in this region. We determined the genotype of DdeI and FokI SNPs, as well as of three other known SNPs, codon 43 (CfoI restricted), codon 41 and codon 105 (TaqI restricted), located respectively in exons 3, 4 and 6 in 62 unrelated subjects from the Italian population. Haplotype distribution for the ten possible pairs of loci were determined by a maximum likelihood procedure. Overall, statistically significant deviations from expected frequencies assuming equilibrium have been observed for the following pairs: FokI/codon 41, FokI/TaqI, codon 41/TaqI (complete association), DdeI/FokI, DdeI/codon 41 and DdeI/TaqI. The data suggest that the FokI area could include sequences operating in strict functional association with sequences included in the codon 41/TaqI area, possibly in order to regulate the F/S isoforms ratio of the A* and *B alleles. Since the ratio between the concentration of the two F and S isoforms is different for the three ACP1 alleles, we suggest that the ACP1 locus has been subjected to strong selective pressure to obtain an optimal alternative splicing mechanism of the *A and *B alleles. The *C variant, on the other hand, seems completely independent from sequences in the FokI/codon 41/TaqI areas, resulting in an inverted F/S ratio compared to that found for *A and *B alleles.