Expanding the phenotypic spectrum and clinical severity associated with WLS gene.

Autor: Abdel-Salam GMH; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt. ghada.abdelsalam@yahoo.com., Afifi HH; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Abdel-Hamid MS; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Ahmed NEB; Orodental Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Taher MB; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., El-Kamah G; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Thiele H; Cologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany., Nürnberg PN; Cologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany., Bolz HJ; Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany.; Senckenberg Centre for Human Genetics, Dr. Senckenbergische Stiftung, 60314, Frankfurt am Main, Germany.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2023 Sep; Vol. 68 (9), pp. 607-613. Date of Electronic Publication: 2023 Apr 28.
DOI: 10.1038/s10038-023-01152-2
Abstrakt: WLS (Wnt ligand secretion mediator or Wntless) orchestrates the secretion of all Wnt proteins, a family of evolutionary conserved proteins, involved in Wnt signaling pathway that has many essential biological functions including the regulation of development, cell proliferation, migration and apoptosis. Biallelic variants in WLS have recently been described in 10 patients with pleiotropic multiple congenital anomalies (MCA) known as Zaki syndrome. We identified a likely disease-causing variant in WLS (c.1579G>A, p.Gly527Arg) in a boy presented with a broad range of MCA including microcephaly, facial dysmorphism, alopecia, ophthalmologic anomalies, and complete soft tissue syndactyly. These features were reminiscent of Zaki syndrome although variable clinical severity was observed. In a detailed clinical assessment, our patient also displayed microphthalmia, dental anomalies, skeletal dysplasia with spontaneous fractures and Dandy-Walker malformation. As such, we extend the phenotype linked to Zaki syndrome. This study further highlights the importance of a thorough clinical evaluation to delineate the phenotypic spectrum associated with WLS variants and suggests that genotype-phenotype correlations due to variant localization seems likely. However, future work on additional patients and more functional studies may give further insights into genotype-phenotype correlations and the complex function of WLS.
(© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Databáze: MEDLINE
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