Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era

被引:0
作者
Carrillo, Isabel Galan [1 ]
Martinez, Liliana Galbis [2 ]
Martinez, Victor [3 ]
Merono, Susana Roca [4 ]
Ramos, Fernanda [1 ]
Rodriguez, Juan David Gonzalez [5 ]
Fernandez, Juan Pinero [6 ]
Navarro, Encarnacion Guillen [7 ]
机构
[1] Hosp Gen Univ Reina Sofia, Serv Nefrol, Murcia, Spain
[2] Hosp Clin Univ Virgen de la Arrixaca, Ctr Bioquim & Genet Clin, Murcia, Spain
[3] Hosp Clin Univ Virgen de la Arrixaca, Serv Nefrol, Murcia, Spain
[4] Hosp Gen Univ Santa Lucia, Serv Nefrol, Cartagena, Murcia, Spain
[5] Hosp Gen Univ Santa Lucia, Serv Pediat, Secc Nefropediat, Cartagena, Murcia, Spain
[6] Hosp Clin Univ Virgen de la Arrixaca, Serv Pediat, Secc Nefropediat, Murcia, Spain
[7] Hosp Clin Univ Virgen de la Arrixaca, Serv Pediat, Secc Genet Med, Murcia, Spain
来源
NEFROLOGIA | 2024年 / 44卷 / 01期
关键词
Hereditary kidney diseases; Autosomal dominant polycystic; kidney disease; Alport syndrome; Genetic diagnosis; Next generation sequencing; (NGS); Multidisciplinary unit; ALPORT-SYNDROME; AUTOSOMAL-DOMINANT; ASSOCIATION; MUTATIONS; VARIANTS;
D O I
10.1016/j.nefro.2022.11.003
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background and objective: Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. Materials and methods: All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. Results: A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family cosegregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy. A total of 101 patients with suspected PKD were also studied, 49.5% had a conclusive genetic result (most frequent gene PKD1), more frequently women, with larger kidney sizes (although 9 patients with normal kidney size confirmed diagnosis). Again, the most predictive characteristic of genetic outcome was family history. Conclusions: The implementation of an NGS panel for HKD, together with the multidisciplinary approach to cases, has improved the diagnostic performance of HKD. In our sample, autosomal dominant Alport syndrome is of highest incidence. Ophthalmological and auditory examinations did not contribute to the diagnosis. We have seen a significant decrease in the indication of renal biopsies thanks to molecular diagnosis. The multidisciplinary approach, with the active participation of nephrologists, paediatricians, clinical and molecular geneticists, with insistence on adequate patient phenotyping and review of their family history, offers a better interpretation of genetic variants, allowing reclassification of the diagnosis of some nephropathies, thus improving their management and genetic advice. (c) 2022 Sociedad Espan similar to ola de Nefrologi ' a. Published by Elsevier Espan similar to a, S.L.U. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
引用
收藏
页码:69 / 76
页数:8
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