Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?

Vasileiou G, Hoyer J, Thiel C, Schaefer JT, Zapke M, Krumbiegel M, Kraus C, Zweier M, Uebe S, Ekici AB, Schneider M, Wiesener M, Rauch A, Faschingbauer F, Reis A, Zweier C, Popp B (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Prenatal Diagnosis Wiley-Blackwell

DOI: 10.1002/pd.5556

Abstract

Objective 17q12 microdeletions containing HNF1B and intragenic variants within this gene are associated with variable developmental, endocrine, and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe prenatal and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to those of previous studies. Methods Prenatal sequencing and postnatal chromosomal microarray analysis were performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B-related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants. Results In a prenatal case, we identified a novel in-frame deletion p.(Gly239del) within the HNF1B DNA-binding domain, a mutational hot spot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions. Literature screening revealed variable reporting of HNF1B-associated clinical traits. Overall, both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up-to-date overview of the mutational spectrum. Conclusions We highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants are necessary for a more accurate risk quantification of prenatal and postnatal clinical features, improving genetic counseling and prenatal decision making.

Authors with CRIS profile

Juliane Hoyer Institute of Human Genetics Christian Thiel Medizinische Fakultät Jan Thomas Schaefer Department of Paediatrics and Adolescent Medicine Steffen Uebe Institute of Human Genetics Arif Bülent Ekici Institute of Human Genetics Michael Schneider Department of Obstetrics and Gynaecology André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Christiane Zweier Medizinische Fakultät Bernt Popp Institute of Human Genetics

Involved external institutions

University of Zurich / Universität Zürich (UZH) CH Switzerland (CH)

How to cite

APA:

Vasileiou, G., Hoyer, J., Thiel, C., Schaefer, J.T., Zapke, M., Krumbiegel, M.,... Popp, B. (2019). Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome? Prenatal Diagnosis. https://doi.org/10.1002/pd.5556

MLA:

Vasileiou, Georgia, et al. "Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?" Prenatal Diagnosis (2019).

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