Background: Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people.
Methods: Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirtythree probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening.
Results: Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population.
Conclusions: The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the "Multisite-3-assay" in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.
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http://dx.doi.org/10.4132/jptm.2022.05.02 | DOI Listing |
PLoS One
January 2025
Department of Public Health, CiST College, Pokhara University, Kathmandu, Nepal.
Background: Poor sleep quality and internet addiction are significant issues affecting adolescents globally, and Nepal is no exception. Several studies have independently assessed the prevalence and associated factors of poor sleep quality and internet addiction among Nepali adolescents and youth, but the relationship between sleep-related attributes and internet addiction remains unexplored. This study aimed to explore the prevalence and contributing factors of poor sleep quality and internet addiction along with the relationship between sleep quality-related attributes and internet addiction.
View Article and Find Full Text PDFInt J Equity Health
January 2025
JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Background: South Asians living in urbanized settings are facing disproportionate cardiovascular burden largely attributable to modifiable risk factors. Given the rapid surge in South Asian population in Hong Kong, this study aims to identify and distinguish clusters of cardiovascular risk profiles among community-dwelling South Asian adults.
Methods: Between June 2022 and December 2023, 1181 South Asian adults were recruited through territory-wide outreach health assessments on lifestyle, psychological distress, obesity, clinical cardiovascular conditions, and sociodemographic factors.
Ocul Immunol Inflamm
January 2025
B.P. Eye Foundation, Hospital for Children Eye ENT and Rehabilitation Services (CHEERS), Bhaktapur, Nepal.
For the past 50 years, significant progress has been made in understanding Seasonal Hyperacute Panuveitis (SHAPU), a mysterious blinding disease first reported in Nepal in 1975. Predominantly affecting Nepalese children, SHAPU occurs cyclically every odd year from September to December. While initially misclassified as endophthalmitis, SHAPU is set apart by its lack of trauma or surgery, failure to grow organisms in most intraocular fluid cultures, and its hallmark presentation of a "white pupil in red eye" with an association with moth exposure.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biology, Faculty of Science and Technology, Mount Royal University, Calgary, AB T3E 6K6, Canada.
With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Medicine and Life Sciences, Institut de Biologia Evolutiva (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain.
Nepal, largely covered by the Himalayan mountains, hosts indigenous populations with distinct linguistic, cultural, and genetic characteristics. Among these populations, the Raute, Nepal's last nomadic hunter-gatherers, offer a unique insight into the genetic and demographic history of Himalayan foragers. Despite strong cultural connections to other regional foragers, the genetic history of this population remains understudied.
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