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Background: Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC., Materials and Methods: Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis., Results: Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor., Conclusion: Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 ( BRCA1/2 ) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population., Materials and Methods: Screening for the four Colombian founder mutations BRCA1 /c.3331_3334delCAAG, BRCA1 /c.5123C>A, BRCA2 /c.2806_2809delAAAC, and BRCA2 /c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR-based restriction fragment length polymorphism analysis, and qualitative real-time PCR. Mutations were confirmed by direct DNA sequencing., Results: The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years., Conclusion: Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro-Colombian population., Implications for Practice: Risk reduction intervention programs are needed for women who are found to carry a BRCA1/2 mutation, as is the implementation of prevention programs for patients with inherited breast cancer, to reduce the burden of inherited diseases. With the aim of reducing racial disparities in breast cancer prevention, this study focused on genetic testing and treatment for patients in a minority population with BRCA1/2 mutations., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Locating the source of lumbopelvic-hip pain requires the consideration of multiple clinical pathways. Although low back pain has an incidence of 50% in the adolescent population, the pathophysiology in this population typically differs from that of other age groups. Dynamic mechanical impairments of the hip, such as femoroacetabular impingement, may contribute to the pathogenesis of adolescent low back pain. Eight adolescent male athletes who presented to a single provider with a primary complaint of low back pain with hip pain or motion loss on exam and were ultimately diagnosed with lumbar spondylolysis and dynamic mechanical hip issues between 2009 and 2011 were included. The age at spondylolysis diagnosis ranged from 15 to 19 years (mean ± standard deviation: 16.3 ± 1.3 years). Seven patients had cam-type impingement, whereas one presented with pincer-type impingement. All patients demonstrated either decreased internal rotation at 90 degrees of hip flexion and neutral abduction or pain on the Flexion Adduction Internal Rotation test on at least one of hip. All eight patients were treated initially with 6 weeks of physical therapy consisting of attempted restoration of hip motion and the graduated progression of hip and spine stabilization exercises. Five patients (62.5%) returned to sport at an average of 11.2 weeks (range: 6-16 weeks). For three patients (37.5%), hip pain and motion loss persisted, thus requiring surgery. All subjects had symptoms for at least 6 weeks, with 6 months as the longest duration. This report is the first documented series of adolescent athletes with co-diagnoses of spondylolysis and femoroacetabular impingement. Study Information: This retrospective case series was approved by the Institutional Review Board at Hospital for Special Surgery.

Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency., (Copyright © 2017 by the Genetics Society of America.)