Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?
Prenat Diagn
; 39(12): 1136-1147, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31498910
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Natal
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Cromossomos Humanos Par 17
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Deleção Cromossômica
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Análise em Microsséries
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Doenças Renais Císticas
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Fator 1-beta Nuclear de Hepatócito
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Child
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Female
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Humans
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Male
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Newborn
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Pregnancy
Idioma:
En
Revista:
Prenat Diagn
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha