scholarly journals Identification of Novel Nonsense Mutations in Iranian patients suffering from autosomal dominant polycystic kidney disease

2019 ◽  
Author(s):  
Fatemeh Khadangi ◽  
Adam Torkamanzehi ◽  
Mohammad Amin Kerachian
Keyword(s):  
Kidney Disease ◽  
Genetic Analysis ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Iranian Patients

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD) is the predominant type of inherited kidney disorder, which occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging; however, molecular genetic analysis needs to be implicated to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the diagnosis is uncertain, particularly in simplex cases (i.e., a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the likelihood of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was isolated from blood samples from 26 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using suitable primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing.Results: The results of DNA sequencing in the patients showed that exons 35, 36 and 37 were non- polymorphic, while most mutations had occurred in exons 44 and 45. Only in two patients, exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and non-synonymous types. Conclusion: In this study, we present nine novel mutations/polymorphisms in PKD1. These data will contribute to an improved diagnostic and genetic counseling in clinical settings. Keywords: Autosomal dominant polycystic kidney disease; PKD1; mutational analysis; Iranian

scholarly journals Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Khadangi ◽  
Adam Torkamanzehi ◽  
Mohammad Amin Kerachian
Keyword(s):  
Kidney Disease ◽  
Genetic Analysis ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Iranian Patients

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e. a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing. Results The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and synonymous types. Conclusion In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings.

scholarly journals Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease

2020 ◽  
Author(s):  
Fatemeh Khadangi ◽  
Adam Torkamanzehi ◽  
Mohammad Amin Kerachian
Keyword(s):  
Kidney Disease ◽  
Genetic Analysis ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Pkd1 Gene ◽  
Autosomal Dominant Polycystic Kidney ◽  
Iranian Patients

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e., a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing. Results: The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and non-synonymous types. Conclusion: In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings.

Mutation variability at polycystic kidney disease detected by NGS

2020 ◽  
pp. 25-37
Author(s):  
Н.Н. Вассерман ◽  
А.В. Поляков
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Target Genes ◽  
Autosomal Dominant ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Parallel Sequencing ◽  
Pkd1 Gene ◽  
Autosomal Dominant Polycystic Kidney

Поликистозная болезнь почек (ПП) является клинически и генетически гетерогенной группой заболеваний, может наследоваться как аутосомно-доминантно (АД), так и аутосомно-рецессивно (АР). К развитию АР ПП приводят мутации в гене PKHD1. Большинство мутаций при АД ПП находят в гене PKD1 (80-85%). Примерно в 15% случаев мутации выявляют в гене PKD2. Клиническое и генетическое разнообразие ПП требует поиска мутаций в нескольких генах, поэтому он является трудоемким, дорогостоящим и требует много времени. Метод массового параллельного секвенирования (МПС) позволяет проводить поиск мутаций в нескольких генах одновременно независимо от их размера. Проведен поиск мутаций в 254 семьях с ПП методом МПС с использованием панели, включающей гены PKHD1, PKD1, PKD2, HNF1B и GANAB. Два варианта в гене PKHD1 было идентифицировано в 49 семьях (19%), один вариант найден в 9 случаях (3,5%); в гене PKD1 обнаружено 62 варианта (24,5%), в гене PKD2 - 6 вариантов (2,5%), в гене HNF1B - 9 вариантов (3,5%). В 119 семьях, что составило 47%, мутации найдены не были. У больных из семей с генеалогически установленным АД типом наследования в большинстве случаев (39 из 66; 59%) выявлены варианты в гене PKD1, приводящие к ПП. Из 59 изолированных случаев ПП в 17% (10 человек) идентифицированы 2 варианта в гене PНKD1, в 20% (12 человек) - в гене PKD1. При неизвестном типе наследования (129 случаев) в 29,5% (38 чел.) найдены 2 варианта в гене PНKD1, в 8,5% (11 чел.) - в гене PKD1, в 3% (4 чел.) - в гене PKD2, в 4% (5 чел.) - в гене HNF1B. Таким образом, МПС относительно быстро позволяет проводить молекулярно-генетический анализ одновременно в нескольких генах у больных с признаками ПП. Polycystic kidney disease is a heterogeneous group of autosomal dominant or autosomal recessive disorders with age of manifestation varying from prenatal period to adulthood. Autosomal recessive polycystic kidney disease is caused by mutations in the PKHD1 gene. Approximately 85% of all autosomal dominant polycystic kidney disease cases are caused by mutations in the PKD1 gene, and around 15% - by mutations in the PKD2 gene. All these genes are large, and mutations were found to be scattered throughout the genes without any clustering. Therefore, mutation detection requires a lot of time, money, and effort. Due to clinical and genetic diversity of polycystic kidney disease, the search for mutations has to be carried out in several genes. Mass parallel sequencing (MPS) allows to analyze several genes simultaneously regardless of their size. 254 families with polycystic kidney disease were examined using mass parallel sequencing with a gene panel that included PKHD1, PKD1, PKD2, HNF1B and GANAB. Two variants in PKHD1 were found in 49 families (19%), one variant - in 9 families (3.5%); in PKD1 62 variants were detected (24.5%), in PKD2 - 6 variants (2.5%), in HNF1B - 9 variants (3.5%). In 119 families (47%) there were no mutations in the target genes. Among 66 patients from families with autosomal dominant polycystic kidney disease, 39 patients (59%) had mutations in the PKD1 gene. Out of 59 sporadic cases, 10 patients (17%) had 2 variants in PНKD1, 12 patients (20%) - in PKD1. 38 patients (29.5%) out of 129 patients with unknown type of inheritance had 2 variants in PНKD1, 11 patients (8.5%) - in PKD1, 4 patients (3%) - in PKD2, 5 patients (4%) - in HNF1B. Mass parallel sequencing allows to carry out relatively rapid molecular genetic analysis of several genes simultaneously for patients with symptoms of polycystic kidney disease.

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