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Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.
RESUMO
Introduction: Aggrecanopathies are rare disorders associated with idiopathic short stature. They are caused by pathogenic changes in the ACAN gene located on chromosome 15q26. In this study, we present a case of short stature caused by mutations in the ACAN gene. Case Presentation: A 3-year-3-month-old male patient was referred to us because of his short stature. Physical examination revealed proportional short stature, frontal bossing, macrocephaly, midface hypoplasia, ptosis in the right eye, and wide toes. When the patient was 6 years and 3 months old, his bone age was compatible with 7 years of age. The patient underwent clinical exome sequencing and a heterozygous nonsense c.1243G>T, p.(Glu415*) pathogenic variant was detected in the ACAN gene. The same variant was found in his phenotypically similar father. Our patient is the second case with ptosis. Discussion: ACAN gene mutation should be considered in the differential diagnosis of patients with idiopathic short stature. The development and widespread use of next-generation sequencing technology has increased the diagnostic and treatment possibilities.
