Clinical impact of genomic testing in patients with suspected monogenic kidney disease.,Genetics in Medicine

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Clinical impact of genomic testing in patients with suspected monogenic kidney disease.
Genetics in Medicine ( IF 8.8 ) Pub Date : 2020-09-17 , DOI: 10.1038/s41436-020-00963-4
Kushani Jayasinghe _{1,

2,

3,

4} , Zornitza Stark _{3,

4,

5,

6} , Peter G Kerr _{1,

2} , Clara Gaff _{7,

8} , Melissa Martyn _{3,

7} , John Whitlam ₉ , Belinda Creighton ₁₀ , Elizabeth Donaldson ₁₁ , Matthew Hunter _{12,

13} , Anna Jarmolowicz ₁₁ , Lilian Johnstone _{13,

14} , Emma Krzesinski _{12,

13} , Sebastian Lunke ₆ , Elly Lynch ₇ , Kathleen Nicholls ₁₅ , Chirag Patel _{4,

16} , Yael Prawer ₁₂ , Jessica Ryan _{1,

2} , Emily J See ₁₇ , Andrew Talbot ₁₅ , Alison Trainer _{11,

17} , Rigan Tytherleigh _{3,

7} , Giulia Valente ₁₈ , Mathew Wallis _{18,

19} , Louise Wardrop _{3,

4} , Kirsty H West _{7,

11} , Susan M White _{5,

6} , Ella Wilkins _{3,

6} , Andrew J Mallett _{3,

4,

20,

21} , Catherine Quinlan _{3,

4,

5,

22}

Affiliation

Department of Nephrology, Monash Medical Centre, Melbourne, Australia.
School of Clinical Sciences, Monash University, Melbourne, Australia.
Murdoch Children's Research Institute, Melbourne, Australia.
The KidGen Collaborative, Australian Genomics Health Alliance, Melbourne, Australia.
Department of Pediatrics, University of Melbourne, Melbourne, Australia.
Victorian Clinical Genetics Services, Melbourne, Australia.
Melbourne Genomics Health Alliance, Melbourne, Australia.
Department of Pediatrics, Faculty of Medicine Dentistry & Health Sciences, The University of Melbourne, Melbourne, Australia.
Department of Nephrology, Austin Health, Melbourne, Australia.
Cancer Genetics and Genomics Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
Department of Genomic Medicine, Royal Melbourne Hospital, Melbourne, Australia.
Monash Genetics, Monash Health, Melbourne, Australia.
Department of Pediatrics, Monash University, Melbourne, Australia.
Department of Nephrology, Monash Children's Hospital, Melbourne, Australia.
Department of Nephrology, Melbourne Health, Melbourne, Australia.
Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Department of Medicine, University of Melbourne, Melbourne, Australia.
Clinical Genetics Service, Austin Health, Melbourne, Australia.
School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Kidney Health Service and Conjoint Renal Research Laboratory, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Institute for Molecular Bioscience and Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Department of Pediatric Nephrology, Royal Children's Hospital, Melbourne, Australia.

Purpose

To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease.

Methods

We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia.

Results

ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%).

Conclusion

In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

中文翻译：

基因组检测对疑似单基因肾病患者的临床影响。

目的

确定外显子组测序 (ES) 对疑似单基因肾病患者的诊断率和临床影响。

方法

我们在澳大利亚墨尔本四家三级医院的多学科肾脏遗传学诊所评估的 204 名患者的前瞻性确定队列中进行了临床认可的单胎 ES。

结果

ES 确定了 80 名（39%）患者的分子诊断，包括 35 种不同的遗传疾病。就诊时年龄较小与 ES 诊断独立相关（p < 0.001）。在被诊断的人中，31/80 (39%) 的临床诊断发生了变化。47/80 (59%) 认为 ES 诊断有助于管理，包括 10/80 (13%) 不需要诊断性肾活检，35/80 (44%) 改变监测和改变治疗计划在 16/80 (20%)。在先证者的管理没有改变的情况下，ES 结果对 26/33 (79%) 的家庭成员的管理有影响。随后向 40/80 个家庭 (50%) 提供了级联测试。