Marker Kromozomlu Olguların İleri Moleküler Genetik Analizleri ile Genotip - Fenotip Korelasyonu

Abstract

Marker chromosomes are defined as ?structurally abnormal chromosomes which cannot be identified unambiguously by conventional cytogenetics alone, and are equal in size to or smaller than a chromosome 20 of the same metaphase spread? and named as sSMC (small Supernumerary Marker Chromosomes). Marker chromosomes are present in 0.075% of unselected prenatal samples and in 0.044% of newborns. 0.125% of people with problems in conceiving are sSMC carriers and this rate is 0.28% in intellectually disabled patients. Seven cytogenetically described marker chromosome cases with intellectual disability and dysmorphic findings are examined in detail. The origin, structure and start-end position of marker chromosomes determined with Affymetrix® 250K SNP array and SubcenM-FISH (Subcentromere-specific multicolor FISH) analyses. The structures of marker chromosomes are revealed as tetrasomy 18p in 4 patients, inv dup(15) in 2 patients and min(15) in 1 patient. Intellectually disability, microcephaly, strabismus, typical dysmorphic face appearance (prominent nasal root, ear anomalies, microstomia) were common clinical findings in tetrasomy 18p patients. In sSMC(15) patients the common clinical findings were determined as developmental delay, mild intellectually disability, seizures, behavioral disorders and speech delay. Contribution to literature was made by comparing clinical findings of marker chromosome patients with the limited published cases in the literature. Follow-up protocols for patients with tetrasomy 18p and sSMC(15) were established. The functions of genes on chromosome 15 were investigated and we considered that the clinical findings of sSMC(15) patients are associated with copy number alteration of dosage-sensitive genes on marker chromosome.