Fetal brain arrest broadens the spectrum of WDR81-related developmental brain malformations.

Autor: Abdel-Hamid MS; Human Genetics and Genome Research Division, Medical Molecular Department, National Research Centre, Cairo, Egypt., Sabry S; Human Genetics and Genome Research Division, Biochemical Genetics Department, National Research Centre, Cairo, Egypt., Abdel-Ghafar SF; Human Genetics and Genome Research Division, Medical Molecular Department, National Research Centre, Cairo, Egypt., El-Dessouky SH; Division of Human Genetics and Genome Research, Department of Prenatal Diagnosis & Fetal Medicine, National Research Centre, Cairo, Egypt., Abdel-Salam GMH; Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, El-Tahrir Street, Dokki, Cairo, Egypt. ghada.abdelsalam@yahoo.com.
Jazyk: angličtina
Zdroj: Neurogenetics [Neurogenetics] 2021 Oct; Vol. 22 (4), pp. 287-295. Date of Electronic Publication: 2021 Aug 02.
DOI: 10.1007/s10048-021-00665-2
Abstrakt: Fetal brain arrest is an extremely rare genetic disorder that was described in few patients and encompasses very unique findings of underdeveloped cerebral hemispheres in association with collapsed skull bones. Based on the recurrence among sibs, an autosomal recessive mode of inheritance was proposed; however, no causative gene was identified so far. Here, we report the identification of biallelic variants in the WDR81 gene in two unrelated families (4 patients) with fetal brain arrest including the originally described family and an additional new family. Two homozygous variants were identified: a new missense (c.1157 T > C, p.Val386Ala) and a previously described frameshift variant, c.4668_4669delAG (p.Gly1557AspfsTer16). We assessed the expression of WDR81 at the protein level by western blot analysis using primary skin fibroblast cultures established from the patient with the missense variant and noticed that WDR81 expression was significantly reduced in comparison to normal control confirming the pathogenicity of this variant. Our findings confirm the involvement of WDR81 in the pathogenesis of fetal brain arrest syndrome and suggest that fetal brain arrest represents the severe end of the spectrum phenotypes caused by pathogenic variants in WDR81. In addition, we reviewed the clinical and molecular data on WDR81-related disorders and phenotype/genotype correlations.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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