Low Prevalence of the Four Common Colombian Founder Mutations in BRCA1 and BRCA2 in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer.

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.

Análisis mutacional del gen MSX1 en pacientes con FLPNS e hipodoncia / Mutation analysis of MSX1 gene in patients with NSCLP and hypodontia

Introducción. La etiología de la hendidura labio-palatina es compleja e involucra factores genéticos y ambientales. Además de la hendidura, numerosos estudios han reportado la presencia de anomalías dentales en asociación con varias formas de hendidura labial,palatina o ambas; entre estas anomalías se ha encontrado la prevalencia de agenesia dental. La idea de que los mismos factores etiológicos que causan la formación de la hendidura afectan el desarrollo de la dentición, es apoyada por varios autores que proponen al genMSX1 como candidato para estos dos fenotipos. Una mutación nonsense (Ser104stop) en el exon 1 del gen MSX1 se encontró en una familia danesa, en la que unos miembros presentaban agenesia dental o hendidura palatina y otros presentaban las dos entidadesasociadas. A pesar de que se han realizado varios estudios sobre anomalías dentales en pacientes con hendidura labio-palatina y existen estudios que confirman a MSX1 como ungen candidato tanto para hipodoncia como para hendiduras oro-faciales, la interpretación de los resultados ha sido muy compleja. Objetivo. Determinar la presencia de la mutación reportada en pacientes colombianos con hendidura labio-palatina e hipodoncia. Materiales y métodos. Se analizaron 30 pacientes, 22 con hendidura labio-palatina y 8 sólo con hipodoncia, y 60 controles sanos, mediante exámenes clínicos y radiográficos; se les tomaron muestras de sangre por venopunción, se extrajo el ADN y se realizó amplificación por la técnica de PCR del exón 1. Posteriormente, se llevó a cabo un análisis de restricción. Resultados. De los pacientes con hendidura labio-palatina, 16 presentaron agenesias dentalesfuera y dentro del área de hendidura, la mayoría fueron laterales y premolares superiores. La mayoría de los pacientes con hipodoncia únicamente, presentaron ausencias de incisivos. Además, presentaron otras anomalías dentarias, como micrognatismo, dientes supernumerarios y prognatismo mandibular...

Introduction: The etiology of non-syndromic cleft lip palate is complex and involves genetic and environmental factors. Additional to the fissure itself, numerous studies have reported the presence of dental anomalies with various forms of cleft lip, cleft palate or both. The prevalence of dental agenesis has been found within these anomalies. The idea that the same etiology factors which cause the formation of the cleft affect the dental development is supported by various authors who propose the MSX1 gene to be the candidate for these two phenotypes. A nonsense mutation in the exon 1 of the MSX1 gene was found in a Danish family in which one of the members presented dental agenesis and/or cleft palate and others presented both entities. Although various studies have been associated reported with respect to dental anomalies in patients with nonsyndromic cleft lip palate and there are studies which confirm MSX1 as a candidate gene for hypodontia and orofacial fissures, the interpretation of the results has been very complex.Objective: To determine the presence of the mutation reported in Colombian patients with nonsyndromic cleft lip palate and hypodontia. Materials and methods: 30 patients, 22 with non-syndromic cleft lip palate and 8 with only hypodontia and 60 healthy patients were clinically and radiographically analyzed. Blood samples were taken through venopunction, the DNA was extracted and the PCR technique was utilized. Afterwords, the restriction analysiswas carried out...