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Diagnosis of microdeletion syndromes using the FISH method in Croatia

Cytogenetics has low resolution power and chromosome anomalies smaller than 10 Mb cannot be detected by routine cytogenetic methods. Specific clinical entities known as "contigous gene syndromes" are difficult to diagnose at that resolution level and FISH is the method of choice for the diagnosis of such microdeletion syndromes (MDS). In this report we evaluate the efficiency of the diagnostic approach that starts with a clinical examination, followed by cytogenetic and FISH analysis in a group of patients who were suspected of having MDS and referred to cytogenetic laboratory from 2000 to 2003. The study included 65 children and three adults. The analysis was performed on slides obtained by blood culture and treated for high-resolution GTG- banding. FISH method with LSI probe for TUPLE1 (62 cases), SNRPN (2 cases), LIS1 (1 child), SMS (3 cases) and ELN (1 child) region was performed according to the manufacturers suggestions (Vysis). Cytogenetic analysis revealed normal karyotypes in all but one child with structural aberration of chromosome 18 and suspected of DiGeorge sy. FISH analysis revealed hemizygosity for 22q11 in 5 (8%) out of 62 persons and deletion of SNRPN in both patients suspected for Prader-Willi sy. Deletion of ELN locus was identified in one patient originally suspected for DiGeorge sy. Reevaluation revealed microdeletion of 7q11.2 and Williams sy. was diagnosed. This study gives additional evidence that: 1. FISH is the method of choice for MDS detection. 2. To disclose eventual major chromosomal aberrations we consider cytogenetic analysis an important step in the evaluation of patients suspected of having MDS. 3. Although clinical presentation of different MDS are well known, there is considerable variability and overlapping of the phenotype manifestations. Their detection thus requires additional tests and stepwise reevaluation of patients in order to plan a rational approach to the diagnosis of submicroscopic aberrations.

cytogenetics; FISH; microdeletion syndromes

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