Abstract
Aim and Introduction
Identification of abnormal kidneys in the fetus may lead to termination of the pregnancy and raises questions about the underlying cause and recurrence risk in future pregnancies.
In this study, we investigate the effectiveness of targeted next generation sequencing in fetuses with prenatally detected kidney anomalies in order to uncover genetic explanations and assess recurrence risk. Also, we aim to study the relation between genetic findings and post mortem kidney histology.
Methods
The study comprises fetuses diagnosed prenatally with bilateral kidney anomalies that have undergone postmortem examination.
The approximately 110 genes included in the targeted panel were chosen on the basis of their potential involvement in embryonic kidney development, cystic kidney disease, or the renin-angiotensin system.
DNA was extracted from fetal tissue samples or cultured chorion villus cells, aminocytes, or fibroblasts. Data analysis was performed using CLC Genomics workbench, publicly available databases, and prediction tools.
The Regional Ethical Committee approved the study.
Results
Samples from 61 fetuses from 57 families were included in the study.
Two fetuses had mutations in the nephronophthisis associated gene, TMEM67 and six fetuses had mutations in kidney developmental genes. For these fetuses kidney histology is presented.
Conclusion and Perspectives
In eight (14%) fetuses we identified a likely genetic cause of the kidney anomalies.
Ten fetuses from eight families, in which no mutations were identified, have been selected for exome sequencing in order to uncover novel genes associated to fetal kidney anomalies.
Identification of abnormal kidneys in the fetus may lead to termination of the pregnancy and raises questions about the underlying cause and recurrence risk in future pregnancies.
In this study, we investigate the effectiveness of targeted next generation sequencing in fetuses with prenatally detected kidney anomalies in order to uncover genetic explanations and assess recurrence risk. Also, we aim to study the relation between genetic findings and post mortem kidney histology.
Methods
The study comprises fetuses diagnosed prenatally with bilateral kidney anomalies that have undergone postmortem examination.
The approximately 110 genes included in the targeted panel were chosen on the basis of their potential involvement in embryonic kidney development, cystic kidney disease, or the renin-angiotensin system.
DNA was extracted from fetal tissue samples or cultured chorion villus cells, aminocytes, or fibroblasts. Data analysis was performed using CLC Genomics workbench, publicly available databases, and prediction tools.
The Regional Ethical Committee approved the study.
Results
Samples from 61 fetuses from 57 families were included in the study.
Two fetuses had mutations in the nephronophthisis associated gene, TMEM67 and six fetuses had mutations in kidney developmental genes. For these fetuses kidney histology is presented.
Conclusion and Perspectives
In eight (14%) fetuses we identified a likely genetic cause of the kidney anomalies.
Ten fetuses from eight families, in which no mutations were identified, have been selected for exome sequencing in order to uncover novel genes associated to fetal kidney anomalies.
| Original language | English |
|---|---|
| Publication date | May 2016 |
| Number of pages | 1 |
| Publication status | Published - May 2016 |
| Event | European Society of Human Genetics Conference 2016 - Barcelona, Spain Duration: 21 May 2016 → 24 May 2016 |
Conference
| Conference | European Society of Human Genetics Conference 2016 |
|---|---|
| Country/Territory | Spain |
| City | Barcelona |
| Period | 21/05/2016 → 24/05/2016 |