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Войти в исследования Nephrology (Carlton, Vic.) · 2026
Genetic Spectrum and Family-Based Cascade Screening in Vietnamese Families With Autosomal Dominant Polycystic Kidney Disease.
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Thuy Nguyen Thi An, Tran Van Khanh, Nguyen Ngoc Lan, Phuong Le Thi, Vu Thi Ha, Cao Thi Nhu, Do Truong Minh, Nguyen Phan Long, Tran Thao Linh, Dang Tran Nhat Minh, Tran Thinh Huy, Nghiem Trung Dung
Аннотация
AIM: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited causes of kidney failure. We performed a whole-exome sequencing study that aimed to characterize the spectrum of PKD1 and PKD2 variants in a Vietnamese ADPKD cohort and to evaluate the clinical utility of family-based cascade genetic testing.
METHODS: This cross-sectional descriptive study included 40 unrelated patients with clinically diagnosed polycystic kidney disease. Variants were identified in probands using whole-exome sequencing. Family-based genetic testing was subsequently performed using Sanger sequencing in 104 relatives. Cascade screening was restricted to families with pathogenic or likely pathogenic variants, whereas variant of uncertain significance families were evaluated separately through segregation analysis to support variant interpretation and potential reclassification. Clinical and genetic characteristics were described and exploratory genotype-phenotype analyses were performed.
RESULTS: Genetic testing identified PKD1 variants in 77.5% of patients, PKD2 variants in 17.5% and no ADPKD-related variants in 5.0%. A total of 37 potentially relevant variants were detected, including 31 in PKD1 (83.8%) and six in PKD2 (16.2%). Nine novel variants were identified. PKD1 carriers were younger than PKD2 carriers (p = 0.029) at the time of evaluation. Apart from this age difference, no other clinical characteristics differed significantly according to gene type or variant class. Cascade screening of 89 relatives from families with pathogenic or likely pathogenic variants revealed that 53 (59.6%) carried the familial variant, whereas 36 (40.4%) did not. Among 53 variant-positive relatives, 34 (64.2%) were symptomatic and 19 (35.8%) were asymptomatic at the time of evaluation. In contrast, no variant-negative relatives showed clinical evidence of ADPKD (p < 0.001). These findings are consistent with autosomal dominant segregation of the familial variant and support the clinical utility of cascade screening.
CONCLUSION: This study expands the known genetic spectrum of ADPKD in Vietnamese families and demonstrates the predominance of PKD1 variants in this cohort. Family-based cascade screening was useful for identifying variant-positive relatives before overt clinical manifestation, thereby supporting earlier surveillance and genetic counselling.
METHODS: This cross-sectional descriptive study included 40 unrelated patients with clinically diagnosed polycystic kidney disease. Variants were identified in probands using whole-exome sequencing. Family-based genetic testing was subsequently performed using Sanger sequencing in 104 relatives. Cascade screening was restricted to families with pathogenic or likely pathogenic variants, whereas variant of uncertain significance families were evaluated separately through segregation analysis to support variant interpretation and potential reclassification. Clinical and genetic characteristics were described and exploratory genotype-phenotype analyses were performed.
RESULTS: Genetic testing identified PKD1 variants in 77.5% of patients, PKD2 variants in 17.5% and no ADPKD-related variants in 5.0%. A total of 37 potentially relevant variants were detected, including 31 in PKD1 (83.8%) and six in PKD2 (16.2%). Nine novel variants were identified. PKD1 carriers were younger than PKD2 carriers (p = 0.029) at the time of evaluation. Apart from this age difference, no other clinical characteristics differed significantly according to gene type or variant class. Cascade screening of 89 relatives from families with pathogenic or likely pathogenic variants revealed that 53 (59.6%) carried the familial variant, whereas 36 (40.4%) did not. Among 53 variant-positive relatives, 34 (64.2%) were symptomatic and 19 (35.8%) were asymptomatic at the time of evaluation. In contrast, no variant-negative relatives showed clinical evidence of ADPKD (p < 0.001). These findings are consistent with autosomal dominant segregation of the familial variant and support the clinical utility of cascade screening.
CONCLUSION: This study expands the known genetic spectrum of ADPKD in Vietnamese families and demonstrates the predominance of PKD1 variants in this cohort. Family-based cascade screening was useful for identifying variant-positive relatives before overt clinical manifestation, thereby supporting earlier surveillance and genetic counselling.