Frequency and distribution of BRCA1/BRCA2 large genomic rearrangements in Turkish population with breast cancer.

Germline mutations in BRCA1 and BRCA2 genes are mainly responsible for breast and/or ovarian cancer patients. Most of the mutations in these genes are single nucleotide changes or deletions/insertions of small numbers of bases, while a minority of mutations in these genes are large genomic rearrangements (LGRs). The frequency of LGRs in the Turkish population is not clearly known. Also insufficient awareness of the importance of LGRs in breast and/or ovarian cancer development can lead to some disruptions in patient management. So, we aimed to determine the frequency and distribution of the LGRs in the BRCA1/2 genes in the Turkish population. We investigated rearrangements of BRCA genes using multiplex ligation-dependent probe amplification (MLPA) analysis in 1540 patients with a personal and/or family history of breast and/or ovarian cancer or who had familial known large deletion/duplication and applied for segregation. The estimated overall frequency of LGRs in our group was 3,4% (52/1540) with 91% in BRCA1 gene and 9% in BRCA2 gene. 13 different rearrangements were detected (10 BRCA1, 3 BRCA2). To the best our knowledge, BRCA1 exon 1-16 duplication and BRCA2 exon 6 deletion have not been previously reported before. Our study results supported that the detection of rearrangements in BRCA genes is of great importance and it should be planned routinely in patients whose mutations cannot be detected by sequence analysis in screening programs.

An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey.

Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism, mostly caused by PAH gene variants. The aim of this study was to identify the frequency of PAH gene variants in Turkish population with PKU. In 433 patients with PKU, PAH gene was examined using next generation sequencing (NGS) method. IVS10- 11G>A, p.R261Q, p.A300S, p.A403V, and p.T380 variants, which are the most common variants in this study, constituted 45,9% of the variants in our study. Nine novel variants p.A34V, K73Qfs*4, R157H, R261S, p.T266I, p.S310P, T328A, p.F351I, and K363N were identified. This study determines the most common PAH variants in Turkey and shows that PKU can be screened before marriage with the screening kits. Identification of the PAH gene variant spectrum is important for early diagnosis, understanding molecular mechanisms, clinical follow-up, treatment, and genetic counseling. And the novel variants found this study are important for further studies.