title: Molecularly proven mosaicism in phenotypically normal parent of a girl with Freeman-Sheldon Syndrome caused by a pathogenic MYH3 mutation.
abstract: We report a case of a female child who has classical Freeman-Sheldon syndrome (FSS) associated with a previously reported recurrent pathogenic heterozygous missense mutation, c.2015G > A, p. (Arg672His), in MYH3 where the phenotypically normal mother is a molecularly confirmed mosaic. To the best of our knowledge, this is the first report in the medical literature of molecularly confirmed parental mosaicism for a MYH3 mutation causing FSS. Since proven somatic mosaicism after having an affected child is consistent with gonadal mosaicism, a significantly increased recurrence risk is advised. Parental testing is thus essential for accurate risk assessment for future pregnancies and the use of new technologies with next generation sequencing (NGS) may improve the detection rate of mosaicism. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hague
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Delon
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Brugger
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Howard
authors.initials: H
authors.lastname: Martin
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.affiliation: Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Soo-Mi
authors.initials: SM
authors.lastname: Park
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001299:Audiometry; D055028:Comparative Genomic Hybridization; D003394:Craniofacial Dysostosis / Q000175:diagnosis* / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009030:Mosaicism; D009154:Mutation; D010641:Phenotype; D010808:Physical Examination
chemical_list: D003598:Cytoskeletal Proteins; C510594:MYH3 polypeptide, human
keywords: Freeman-Sheldon syndrome; MYH3 gene; arthrogryposis; mosaic; whistling-face syndrome