Genetic diagnosis of autosomal dominant polycystic kidney disease by targeted capture and next-generation sequencing: Utility and limitations

Qi, Xiao-Ping; Du, Zhenfang; Ma, Juming; Chen, Xiaoling; Zhang, Qing; Fei, Jun; Wei, Xiaoming; Dong, Chen; Ke, Haiping; Liu, Xuanzhu; Li, Feng; Chen, Zhenguang; Su, Zheng; Jin, Hang-Yang; Liu, Wenting; Zhao, Yan; Jiang, Huling; Lan, Zhangzhang; Li, Pengfei; Fang, Mingyan; Dong, Wei; Zhang, Xianning

doi:10.1016/j.gene.2012.12.060

Cited by 37 publications

(37 citation statements)

References 46 publications

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“…These studies [13][14][15][16][17][18] further promoted the gene diagnosis technology development and progress of ADPKD. Thus, more and more studies about gene diagnosis of ADPKD provide more possibility for us to the early diagnosis of ADPKD.…”

Section: Discussionmentioning

confidence: 97%

Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings

Qian

et al. 2015

Renal Failure

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Autosomal dominant polycystic kidney disease (ADPKD) is a serious genetic disorder that can lead to chronic renal disease. Protein dysfunction caused by mutations in the genes polycystic kidney disease 1 (PKD1) and polycystic kidney disease 2 (PKD2) is an important factor in the pathogenesis of ADPKD. In the present study, 30 Chinese patients with confirmed diagnosis of ADPKD, based on ultrasound or computerized tomography (CT) findings were selected, and the exon copy numbers of PKD1 and PKD2 were determined using multiplex ligation-dependent probe amplification (MLPA). MLPA identified exon deletion in 1 case, suspected exon deletion in 4 cases, and suspected duplications in 3 cases. One case of suspected exon deletion was confirmed using quantitative real-time polymerase chain reaction (q-PCR) and sequencing (PKD2 exon 8). A missense mutation was observed in 1 case of exon deletion using q-PCR and sequencing (PKD1 exon 40, c.11333 C4A). The cases of suspected duplications were verified by q-PCR, and the copy number of exon 6 of PKD1 in 1 case of suspected duplication was 3.8 times greater than that in normal controls. Our findings provide new insights into ADPKD screening and mark a possibly meaningful step toward improved diagnosis and treatment of patients with ADPKD.

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Section: Discussionmentioning

confidence: 97%

Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings

Qian

et al. 2015

Renal Failure

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“…Con respecto a donantes con historia familiar de ADPKD, dado el polimorfismo en los alelos de PKD1 o PKD2, no son útiles para hacer el diagnós-tico; en nuestro grupo hemos utilizado donantes > de 30 años, con estudios imaginológicos, con un nú-mero de quistes renales aceptados de acuerdo con la edad, factor importante en lo que se basa el diagnós-tico inicial de esta entidad 11,12 . Dado lo impredecible de la evolución de la nefropatía por IgA, nuestro grupo no acepta estos donantes 13,14 .…”

Section: Discussionunclassified

Trasplante renal con donante vivo en Colombia

García¹,

Ceballos²

2015

Rev. Colomb. Nefrol.

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ResumenLa mejor alternativa para el tratamiento del paciente con enfermedad renal crónica (ERC), en G 5, es el trasplante renal, el cual ha disminuido en forma significativa; no solamente en Colombia sino a escala mundial. De las alternativas médico-quirúrgicas, propuestas para ampliar esta oportunidad de tratamiento fueron, inicialmente,los llamados donantes marginales, los cuales rápidamente fueron superados por la incidencia desbordada de esta entidad, con un incremento en la lista de espera y número de muertes de receptores en espera de un órgano. Teniendo en cuenta los excelentes resultados del donante vivo (DV), con sobrevida del injerto cercana al 90%, a los 10 años de seguimiento, secundaria auna mayor compatibilidad de los antígenos de los linfocitos humanos (HLA), facilidad de planear el momento óptimo del trasplante renal (TX), menorfunción retardada del injerto (DGF), con menos costos etc. Sumado a un riesgo peri operatorio mínimo para el donante como lo demuestra Hartman et al., con una mortalidad del 3.1 x 10.000, cuando se utilizan técni-cas de laparoscopia y de control del dolor; hacen del TX con DV una alternativa aceptable en todo el mundo.Contar con políticas y protocolos definidos de donación y de seguimiento, posteriores a la nefrectomía, en la cual el donante pierde el 35% de su función renal, son perentorios. Los estudios iniciales de seguimiento mostraron un riesgo relativo dehipertensión arterial (HTA), proteinuria y ERC, similar alde la población general; lo cual facilito esta práctica médica; pero en los últimos 5 años,se vienen presentando algunos cuestionamientos sobre este riesgo relativo (RR) por un incremento significativo de diabetes mellitus (DM), HTA, enfermedad cardiovascular en el donante al compararlo con población sana.Muzaleet al., en una cohorte comparativa de 96.217 DV, vs. 20.024 pacientes del NHANES III, encontró a los 10 y 15 años una tasa mayor de ERC en DV al compararlos con pacientes sanos; el RRE (significado de la sigla) a los 15 años fue de 30.8 y 3.9 x 10.000, respectivamente. Con respecto a donantes femeninas en edad reproductiva, Amit X et al., pone entela de juicio esta modalidad de donante al encontrar un incremento significativo de HTA y pre eclampsia durante el embarazo de estas mujeres 11% vs. 5% al compararlas con mujeres no donantes.Es por ello que pedimos a las prestadoras de salud y grupos de trasplantes, una evaluación exhaustiva, con protocolos plenamente definidos para evaluar, prevenir y disminuir los riesgos de esta excelente modalidad de tratamiento para los pacientes en estadio grado 5 de la ERC.Objetivo: el objetivo de este artículo es hacer una reflexión amplia y sistemática de los posibles riesgos vs. beneficios ya demostrados de esta modalidad de tratamiento en nuestro medio.

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“…It requires laborious long-range amplifications [12]. Next generation sequencing (NGS) of PKD1 and PKD2 genes have been tried for ADPKD diagnosis [19-21] and using this technique routine genetic diagnostics of ADPKD and a significant reduction in the time and cost could be achieved for simultaneous sequence analysis of ADPKD genes [22]. Despite the abundance of families with ADPKD in the Asian population [23],there are very few published reports in the literature.…”

Section: Introductionmentioning

confidence: 99%

Identification of Three Novel Frameshift Mutations in the PKD1 Gene in Iranian Families with Autosomal Dominant Polycystic Kidney Disease Using Efficient Targeted Next-Generation Sequencing

Ranjzad

Aghdami

Tara

et al. 2018

Kidney Blood Press Res

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Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited cystic kidney diseases caused by mutations in two large multi-exon genes, PKD1 and PKD2. High allelic heterogeneity and duplication of PKD1 exons 1–32 as six pseudo genes on chromosome 16 complicate molecular analysis of this disease. Methods: We applied targeted next-generation sequencing (NGS) in 9 non-consanguineous unrelated Iranian families with ADPKD to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. Results: Here, we determined three different novel frameshift mutations and four previously reported nonsense mutations in the PKD1 gene encoding polycystin1 in heterozygotes. Conclusion: This study demonstrates the effectiveness of NGS in significantly reducing the cost and time for simultaneous sequence analysis of PKD1 and PKD2, simplifying the genetic diagnostics of ADPKD. Although a probable correlation between the mutation types and phenotypic outcome is possible, however for more extensive studies in future, the consideration of renal hypouricemia (RHUC) and PKD1 coexistence may be helpful. The novel frameshift mutations reported by this study are p. Q1997X, P. D73X and p. V336X.

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Genetic diagnosis of autosomal dominant polycystic kidney disease by targeted capture and next-generation sequencing: Utility and limitations

Cited by 37 publications

References 46 publications

Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings

Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings

Trasplante renal con donante vivo en Colombia

Identification of Three Novel Frameshift Mutations in the PKD1 Gene in Iranian Families with Autosomal Dominant Polycystic Kidney Disease Using Efficient Targeted Next-Generation Sequencing

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