Ebru Erzurumluoglu

Unbalanced translocation involving both chromosomes 8q and 15q trisomies are extremely rare events. We present two different cases with unbalanced chromosomal rearrangements both derived from maternal balanced translocations. The first case is a 4 year-old boy with speech delay, dysmorphic facial features (inc. cleft lip/palate), behavioural disturbances and growth retardation, who had partial 8q trisomy and partial 21p monosomy resulting from a maternal t(8;21) reciprocal translocation. The other case is a 2 day-old boy with ventriculomegaly, dysmorphic facial features and heart defects (patent ductus arteriosus and atrial septal defect) who had partial 15q trisomy and partial 9p monosomy resulting from a maternal t(9;15) reciprocal translocation.

Frontotemporal lobar degeneration (FTLD) describes a group of progressive brain disorders. The expansion of a noncoding GGGGCC (G4C2) hexanucleotide repeat in the C9orf72 gene is a major cause of both familial FTLD and amyotrophic lateral sclerosis. The aim of this study was to determine the prevalence of C9orf72 G4C2-repeat expansion in a Turkish population with FTLD and to determine its effects on the phenotype. The G4C2 expansion in the C9orf72 gene was analyzed in 100 cases of FTLD without mutations of the MAPT, PGRN, CHMP2B, VCP, TARDBP, and FUS genes and 100 age-matched healthy controls by using repeat-primed polymerase chain reaction and fragment length analysis techniques. A possible pathogenic repeat (≥30) was found in one of the familial cases (1/33), but none of the sporadic cases. The difference in the allele length between the cases and controls was statistically significant (p < 0.01). Intermediate (20–30) repeats were detected in 4% of our cases. Patients with psychotic symptoms appear to be enriched for intermediate and possibly pathogenic repeats. To determine whether the intermediate and ≥30-repeat allele carriers shared the C9orf72 risk haplotype, we examined rs4879515 and rs3849942 in all samples and family members of patients with possibly pathogenic alleles. We identified at least one risk allele for each single-nucleotide polymorphism in all intermediate and possibly pathogenic repeat carriers. We observed that ≥8 unit repeats were strongly correlated with the tagging risk alleles for both single-nucleotide polymorphisms (p < 0.001). To our knowledge, this is the first study to evaluate C9orf72 G4C2 repeats in Turkish patients with FTLD. The present findings suggest that pathogenic expansions of the C9orf72 repeat are uncommon in Turkish patients with FTLD, but intermediate repeats may be a risk factor for FTLD and act as a genetic modifying factor for psychotic symptoms.

Chromosome microarray analysis is a genome-wide, high-resolution technique that can identify large (5-10Mb) unbalanced chromosome abnormalities detected by conventional cytogenetic methods, as well as submicroscopic deletions and duplications down to 20- to 100kb level. Since the technique has a greater resolution than conventional karyotyping, it has been widely used for routine postnatal genetic diagnosis and there is a growing interest for arrays in the prenatal diagnosis. In this review, use of this technique for the cytogenetic abnormalities detected by classical karyotyping and the advantages or disadvantages of it in prenatal diagnosis have been discussed. In conclusion, array comparative genomic hybridization (aCGH) is informative for; 1) analyses of copy number variants in case of normal karyotype detected in fetuses with multiple or isolated ultrasound abnormalities, 2) determination of risk of copy number changes near the chromosomal breakpoints sites when conventional karyotyping reveals apparently balanced de novo chromo- some rearrangements in fetal materials, 3) analysis of parental origin and uniparental isodisomy characteristics of aberrant chromosomes containing imprinted genes, 4) determination of chromosomal origin, size, genetic content, inheritance mode, and uniparental isodisomy features of de novo euchromatic marker chromosomes.