System analysis of gene mutations and clinical phenotype in Chinese patients with autosomal-dominant polycystic kidney disease

Jin, Meiling; Chen, Zhiqiang; Liao, Yujie; Li, Zuoxiang; Hu, Panpan; Yan, Qi; Yin, Zhiwei; Li, Qinggang; Fu, Ping; Chen, Xiangmei

doi:10.1038/srep35945

Cited by 17 publications

(17 citation statements)

References 32 publications

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“…Definite pathogenic mutations accounted for 69.9% of all identified mutations in the present study, which was comparable to the results from the previously reported 45.1–66.6% in Caucasian populations [8, 17, 31], but higher than the 27.7–52.2% reported in Asian populations [25, 32]. Among the definite pathogenic mutations, the large deletion mutation was a special one that was detected by MLPA analysis [15].…”

Section: Discussionsupporting

confidence: 81%

“…In the current study, the overall detection rate of PKD mutations was 81.7%, which was consistent with the range of 52.3–85.8% reported in previous studies among Chinese populations [21-25]. Neither PKD1 nor PKD2 mutations were found in 22 probands with a clinical manifestation of ADPKD.…”

Section: Discussionsupporting

confidence: 78%

“…Neither PKD1 nor PKD2 mutations were found in 22 probands with a clinical manifestation of ADPKD. A similar phenomenon was also reported in previous studies [22, 25]. Although no PKD mutations were found in these patients, the protein levels of PC1 and PC2 were probably down-regulated by other mechanisms.…”

Section: Discussionsupporting

confidence: 65%

“…Recently, Jin et al [25] reported mutation analysis of PKD1 and PKD2 among 148 ADPKD patients. However, the lack of pedigree analysis in their study limited the possibility to evaluate the pathogenicity of the identified mutations, especially for those probably pathogenic mutations.…”

Section: Discussionmentioning

confidence: 99%

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Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

Xu¹,

Ma²,

Gu³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with mutations in PKD1 or PKD2. This study aimed to identify novel PKD1 and PKD2 mutations in Chinese patients with ADPKD. Methods: Mutational analyses of both PKD genes were performed in 120 Chinese families with inherited ADPKD using long-range PCR and targeted next-generation sequencing approaches. Sanger sequencing was performed to check the positive mutations, while multiplex ligation-dependent probe amplification was adopted to examine those without mutations for the presence of large deletions. Results: A total of 93 mutations in PKD1 and PKD2 were identified in 98 Chinese families with ADPKD inheritance and the detection rate was 81.7% (98/120). The mutation rates of PKD1 and PKD2 were 91.4% (85/93) and 8.6% (85/93), respectively. Among the 93 mutations, 59.1% (55/93) were reported for the first time. A total of 65 mutations (26 nonsense, 33 frameshift, 2 large deletion, and 4 typical splicing mutations) were identified as definite pathogenic mutations. The remaining 28 mutations (21 missense, 3 in-frame deletion, and 4 atypical splicing mutations) were determined as probable pathogenic mutations. In addition, 9 de novo mutations were found by pedigree analysis. Correlation analysis between genotype and phenotype revealed that patients with PKD1 mutations or truncating mutations exhibited the most severe clinical outcome. Conclusion: The newly identified sites for known mutations will facilitate the early diagnosis and prediction of prognosis in patients with ADPKD, and provide fundamental genetic information for clinical intervention to prevent the inheritance of this disease in affected families.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

Xu¹,

Ma²,

Gu³

et al. 2018

Kidney Blood Press Res

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“…With the development of genetic testing technology, it is possible to make a definitive diagnosis before the onset age of a patient. Genotypes can also provide the basis for disease progression and prognosis (Jin et al, ). Based on our research and clinical experience, we designed the diagnosis process for patients with a positive family history (Figure ).…”

Section: Discussionmentioning

confidence: 99%

Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next‐generation sequencing technology

Wang

Shang

et al. 2019

Molec Gen & Gen Med

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Background Polycystic kidney disease (PKD) is the most common hereditary kidney disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare pathogenic genes. Unilateral PKD is rare in clinics, and its association with gene mutations is unclear. Methods Targeted next‐generation sequencing (NGS) was performed to detect the renal ciliopathy‐associated genes (targeted NGS panel including 63 genes) in PKD patients. Results Forty‐eight PKD1 and PKD2 mutation sites were detected in 44 bilateral PKD patients, of which 48 were PKD1 mutation sites (87.5%) and six were PKD2 mutation sites (12.5%). All of which exhibited typical ADPKD. Furthermore, we detected HNF1B heterozygous mutations in three families. Although these three patients showed HNF1B heterozygous mutations, their clinical characteristics differed and showed phenotypic heterogeneity. Conclusions Targeted NGS panel was helpful in detecting typical ADPKD patients and even in non‐typical PKD patients. Macromutation in HNF1B may lead to bilateral PKD. The 16 novel PKD gene mutation sites and two novel PKD2 gene mutation sites discovered in this study have some significance in genetic counseling for ADPKD patients, and increase the number of studied families and expand the mutation database of ADPKD.

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Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

Claus

Snoek

Knoers

et al. 2022

American J of Med Genetics Pt C

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Genetic kidney disease comprises a diverse group of disorders. These can roughly be divided in the phenotype groups congenital anomalies of the kidney and urinary tract, ciliopathies, glomerulopathies, stone disorders, tubulointerstitial kidney disease, and tubulopathies. Many etiologies can lead to chronic kidney disease that can progress to end-stage kidney disease. Despite each individual disease being rare, together these genetic disorders account for a large proportion of kidney disease cases. With the introduction of massively parallel sequencing, genetic testing has become more accessible, but a comprehensive analysis of the diagnostic yield is lacking. This review gives an overview of the diagnostic yield of genetic testing across and within the full range of kidney disease phenotypes through a systematic literature search that resulted in 115 included articles. Patient, test, and cohort characteristics that can influence the diagnostic yield are highlighted. Detection of copy number variations and their contribution to the diagnostic yield is described for all phenotype groups. Also, the impact of a genetic diagnosis for a patient and family members, which can be diagnostic, therapeutic, and prognostic, is shown through the included articles. This review will allow clinicians to estimate an a priori probability of finding a genetic cause for the kidney disease in their patients.

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System analysis of gene mutations and clinical phenotype in Chinese patients with autosomal-dominant polycystic kidney disease

Cited by 17 publications

References 32 publications

Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next‐generation sequencing technology

Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

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