Universität zu Köln

Neitzel, Heidemarie, Varon, Raymonda, Chughtai, Sana, Dartsch, Josephine, Dutrannoy-Toensing, Veronique, Nuernberg, Peter, Nuernberg, Gudrun, Schweiger, Michal, Digweed, Martin, Hildebrand, Gabriele, Hackmann, Karl, Holtgrewe, Manuel, Sarioglu, Nanette, Schulze, Bernt, Horn, Denise and Sperling, Karl (2022). Transmission ratio distortion of mutations in the master regulator of centriole biogenesis PLK4. Hum. Genet., 141 (11). S. 1785 - 1795. NEW YORK: SPRINGER. ISSN 1432-1203

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Abstract

The evolutionary conserved Polo-like kinase 4 (PLK4) is essential for centriole duplication, spindle assembly, and de novo centriole formation. In man, homozygous mutations in PLK4 lead to primary microcephaly, altered PLK4 expression is associated with aneuploidy in human embryos. Here, we report on a consanguineous four-generation family with 8 affected individuals compound heterozygous for a novel missense variant, c.881 T > G, and a deletion of the PLK4 gene. The clinical phenotype of the adult patients is mild compared to individuals with previously described PLK4 mutations. One individual was homozygous for the variant c.881G and phenotypically unaffected. The deletion was inherited by 14 of 16 offspring and thus exhibits transmission ratio distortion (TRD). Moreover, based on the already published families with PLK4 mutations, it could be shown that due to the preferential transmission of the mutant alleles, the number of affected offspring is significantly increased. It is assumed that reduced expression of PLK4 decreases the intrinsically high error rate of the first cell divisions after fertilization, increases the number of viable embryos and thus leads to preferential transmission of the deleted/mutated alleles.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neitzel, Heidemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED Varon, Raymonda UNSPECIFIED UNSPECIFIED UNSPECIFIED Chughtai, Sana UNSPECIFIED UNSPECIFIED UNSPECIFIED Dartsch, Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dutrannoy-Toensing, Veronique UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal UNSPECIFIED UNSPECIFIED UNSPECIFIED Digweed, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hildebrand, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackmann, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Holtgrewe, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Sarioglu, Nanette UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze, Bernt UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Sperling, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-684536
DOI:	10.1007/s00439-022-02461-w
Journal or Publication Title:	Hum. Genet.
Volume:	141
Number:	11
Page Range:	S. 1785 - 1795
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LINKAGE ANALYSIS; TRIPOLAR MITOSIS; HUMAN EMBRYOS; STEM-CELLS; DUPLICATION; CENTROSOMES; FERTILIZATION; REPLICATION; GENERATION; ANEUPLOIDY Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68453