Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre‐ and postnatal diagnostic testing in Germany
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Le résumé fourni par la source
Holoprosencephaly (HPE) has been defined as a distinct clinical entity with characteristic facial gestalt, which may-or may not-be associated with the true brain malformation observed postmortem in autopsy or in pre- or postnatal imaging. Affected families mainly show autosomal dominant inheritance with markedly reduced penetrance and extremely broad clinical variability even between mutation carriers within the same families. We here present advances in prenatal imaging over the last years, increasing the proportion of individuals with HPE identified prenatally including milder HPE forms and more frequently allowing to detect more severe forms already in early gestation. We report the results of diagnostic genetic testing of 344 unrelated patients for HPE at our lab in Germany since the year 2000, which currently with the application of next generation sequencing (NGS) panel sequencing identifies causal mutations for about 31% (12/38) of unrelated individuals with normal chromosomes when compared to about 15% (46/306) using conventional Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). More comprehensive genetic testing by our in house NGS panel sequencing of 10 HPE associated genes (MiSeq™ and NextSeq™500, Illumina, Inc., San Diego, CA) not only allowed to include genes with smaller contribution to the phenotype, but may also unravel additional low frequency or more common genetic variants potentially contributing to the observed large intrafamiliar variability and may ultimately guide our understanding of the individual clinical manifestation of this complex developmental disorder.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre‐ and postnatal diagnostic testing in Germany
- Date Crossref
- 01/06/2018
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Heinrich Heine University Düsseldorf pays non établi dans la noticeUniversité ou école supérieure
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Klinikum Chemnitz pays non établi dans la noticeÉtablissement de santé
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University of Tübingen pays non établi dans la noticeUniversité ou école supérieure
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Center for Human Genetics Regensburg Regensburg Germany pays non établi dans la noticeInstitution
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Medical Faculty pays non établi dans la noticeUniversité ou école supérieure
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Department of Medical Genetics Children's Hospital Chemnitz Chemnitz Germany Department of Medical Genetics pays non établi dans la noticeÉtablissement de santé
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Center for Prenatal Diagnosis and Human Genetics Berlin Germany pays non établi dans la noticeInstitution
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University Hospital Tuebingen Tuebingen Germany Institute of Medical Genetics and Applied Genomics pays non établi dans la noticeUniversité ou école supérieure
Heinrich Heine University Düsseldorf, Klinikum Chemnitz et University of Tübingen, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.