Hinreiner, Sophie and Wieczorek, Dagmar and Mueller, Dietmar and Roedl, Tanja and Thiel, Gundula and Grasshoff, Ute and Chaoui, Rabih and Hehr, Ute (2018) Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre- and postnatal diagnostic testing in Germany. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS, 178 (2). pp. 198-205. ISSN 1552-4868, 1552-4876
Full text not available from this repository. (Request a copy)Abstract
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 post-mortem 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 (TM) and NextSeq (TM) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SONIC HEDGEHOG GENE; MUTATIONS; PHENOTYPE; GENOTYPE; SPECTRUM; LIP; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2020 11:03 |
| Last Modified: | 10 Mar 2020 11:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14455 |
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