Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change Two Novel Mutations and Literature Review
Autor: | Saskia Biskup, Anna Gréen, Alexander Pepler, Katarina Ellnebo, Johan Wahlström, Hartmut Vogt, Jon Jonasson, Anna Sandestig, Margarita Stefanova |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Genetics medicine.medical_specialty biology macromolecular substances medicine.disease Phenotype Developmental disorder 03 medical and health sciences 030104 developmental biology Profilin biology.protein medicine Medical genetics Missense mutation Gene Genetics (clinical) Exome sequencing Actin |
Zdroj: | Molecular Syndromology. 9:259-265 |
ISSN: | 1661-8777 1661-8769 |
Popis: | The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208C>G (p.Pro70Ala) and c.511C>T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB. |
Databáze: | OpenAIRE |
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