Dataset Information

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population.

ABSTRACT: Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations.

SUBMITTER: Mahfoudh W

PROVIDER: S-EPMC3249560 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundTunisia is a North African country of 10 million inhabitants. The native background population is Berber. However, throughout its history, Tunisia has been the site of invasions and migratory waves of allogenic populations and ethnic groups such as Phoenicians, Romans, Vandals, Arabs, Ottomans and French. Like neighbouring and Middle Eastern countries, the Tunisian population shows a relatively high rate of consanguinity and endogamy that favor expression of recessive genetic disorders at relatively high rates. Many factors could contribute to the recurrence of monogenic morbid trait expression. Among them, founder mutations that arise in one ancestral individual and diffuse through generations in isolated communities.MethodWe report here on founder mutations in the Tunisian population by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory.ResultsWe identified two different classes of founder mutations. The first includes founder mutations so far reported only among Tunisians that are responsible for 30 genetic diseases. The second group represents founder haplotypes described in 51 inherited conditions that occur among Tunisians and are also shared with other North African and Middle Eastern countries. Several heavily disabilitating diseases are caused by recessive founder mutations. They include, among others, neuromuscular diseases such as congenital muscular dystrophy and spastic paraglegia and also severe genodermatoses such as dystrophic epidermolysis bullosa and xeroderma pigmentosa.ConclusionThis report provides informations on founder mutations for 73 genetic diseases either specific to Tunisians or shared by other populations. Taking into account the relatively high number and frequency of genetic diseases in the region and the limited resources, screening for these founder mutations should provide a rapid and cost effective tool for molecular diagnosis. Indeed, our report should help designing appropriate measures for carrier screening, better evaluation of diseases burden and setting up of preventive measures at the regional level.

Project description:Background and objectivesModifiable risk factors across the life course play a role in the development of Alzheimer's disease and related dementias (ADRD). Studies have identified racial and ethnic disparities in ADRD risk factors. Few studies have explored the epidemiology of ADRD risk among Middle Eastern and North African (MENA) Americans, largely due to their classification as White in US national health surveys. Our aim was to estimate ADRD risk factors among MENA immigrants compared to US- and foreign-born non-Hispanic White adults.Research design and methodsWe linked cross-sectional 2000-2017 National Health Interview Survey and 2001-2018 Medical Expenditure Panel Survey data (N = 108 695; age ≥ 18 years). Modifiable risk factors for ADRD that were evaluated (yes or no) included less than ninth grade education, hearing loss, traumatic brain injury, hypertension, alcohol use, obesity, smoking, depressive symptoms, marital status, physical inactivity, and diabetes. Bivariate analysis and multivariable logistic regression were conducted. Regression models were adjusted by age and sex.ResultsCompared to US-born White adults, MENA immigrants had higher odds of reporting less than 9th grade education (OR = 1.93; 95% CI = 1.17-3.21) and psychological health concerns (OR = 1.28; 95% CI = 1.06-1.56). Compared to foreign-born White adults, MENA immigrants had higher odds of diabetes (OR = 1.48; 95% CI = 1.06-2.08) and psychological health concerns (OR = 1.24; 95% CI = 1.01-1.54).Discussion and implicationsThe findings provide the first comprehensive look at potentially modifiable risk factors for ADRD among MENA immigrants based on a life course model. Without a racial/ethnic identifier for MENA individuals on a national level, ADRD risk factors among US-born MENA adults and MENA immigrants cannot be examined. More research is needed to explore these risk factors by life stage (early, midlife, and late) to further determine ADRD risk and prevention strategies for MENA Americans.

Dataset Information

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets