Development of diagnostic tools for the analysis of 5p deletions using interphase FISH

Abstract

Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5. Through the phenotypic and molecular analyses of individuals with a subset of the features associated with the syndrome, the genes involved in the syndrome have been mapped to two distinct critical regions. Deletion of a critical region in 5p15.2 results in the distinct facial features associated with the syndrome as well as the severe mental and developmental delay, while a deletion of 5pl 5.3 is associated only with the characteristic cat-like cry, the key diagnostic feature of the syndrome. Therefore, subtle differences in the extent of the 5p deletion can have a profound affect on the prognosis of the patient. In order to more easily differentiate between deletions that lead to the cri-du-chat syndrome phenotype and deletions that lead only to the isolated cat-like cry, we have constructed YAC contigs that span both critical regions. The YAC clones have been used to isolate cosmids mapping to each critical region and cosmids that lie just within the two critical region boundaries have been identified. We report here on the use of these cosmids as probes for fluorescent in situ hybridization experiments on interphase nuclei as a means of more accurately differentiating between small 5p deletions that coincide with a complete cri-du-chat syndrome phenotype and the severe mental and developmental delay that is associated with it and deletions that only delete the distal critical region that coincide with the isolated cat-like cry and a much improved prognosis.

Telomeres: a diagnosis at the end of the chromosomes

“…52 The most typical feature of this syndrome, the cat-like cry, is the result of a subtelomeric deletion located more distal than the deletions that cause the facial features and severe developmental delay in cri du chat syndrome. [53][54][55] However, in the series of Cerruti Mainardi et al 52 the patients with the most distal deletions only had speech delay and no cat-like cry. Rossi et al 12 described a cryptic 5p deletion resulting from a t(4p;5p) in a 15 year old child with moderate mental retardation, triangular face, gingival hypertrophy, prominent incisors, posteriorly angulated ears, and behavioural disturbances.…”

An Integrated Physical Map for the Short Arm of Human Chromosome 5

“…To provide contig nucleation points, 84 STSs generated from flow-sorted chromosome 5 DNA were tested against this pool. All 84 STSs had been localized previously to 1 of 51 bins (average size 1 Mb) on 5p, by somatic cell breakpoint analysis Grady et al 1996;Gersh et al 1997).…”

“…SIGMA was also used to computationally compare our mapping results with the physical maps generated by Hudson et al (1995) and Chumakov et al (1995). All STS markers used for map assembly in this study have been published Grady et al 1996;Gersh et al 1997;Gyapay et al 1996;Hudson et al 1995, this work), and most can be accessed from the appropriate website (below).…”

“…This syndrome results from a deletion of all or part of the short arm of chromosome 5. Previous efforts have yielded YAC contigs Gersh et al 1997) covering the gene regions considered to account for some of the primary features of this syndrome Church et al 1995;Gersh et al 1995). Cri-du-chat breakpoints are known to occur throughout most of the 5p region .…”

Validity of chromosomal aneuploidies testing during pregnancy: A comparison of karyotype, interphase-FISH and QF-PCR techniques

“…Interphase-FISH method accomplished on uncultured cells was developed in 1997 [8,9], which applies Interphase rather than metaphase cultured-cells in metaphase-FISH, is a rather privileged method for rapid and early prenatal aneuploidies screening with high sensitivity and accuracy [10,11]. However, interphase FISH has an implied disadvantage with regard to directly detection of whole chromosomes or chromosome regions, yet sufficient to distinguish between polyploid, monoploid, and diploid cells [12].…”