title: Familial recurrences of FOXG1-related disorder: Evidence for mosaicism.
abstract: FOXG1-related disorders are caused by heterozygous mutations in FOXG1 and result in a spectrum of neurodevelopmental phenotypes including postnatal microcephaly, intellectual disability with absent speech, epilepsy, chorea, and corpus callosum abnormalities. The recurrence risk for de novo mutations in FOXG1-related disorders is assumed to be low. Here, we describe three unrelated sets of full siblings with mutations in FOXG1 (c.515_577del63, c.460dupG, and c.572T > G), representing familial recurrence of the disorder. In one family, we have documented maternal somatic mosaicism for the FOXG1 mutation, and all of the families presumably represent parental gonadal (or germline) mosaicism. To our knowledge, mosaicism has not been previously reported in FOXG1-related disorders. Therefore, this report provides evidence that germline mosaicism for FOXG1 mutations is a likely explanation for familial recurrence and should be considered during recurrence risk counseling for families of children with FOXG1-related disorders.
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Kelly Q
authors.initials: KQ
authors.lastname: McMahon
authors.affiliation: Developmental Neurosciences, UCL-Institute of Child Health, London, United Kingdom.|Department of Neurology, Great Ormond Street Hospital, London, United Kingdom.|Genetics and Genomics Medicine, UCL-Institute of Child Health, London, United Kingdom.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papandreou
authors.affiliation: University of Buffalo School of Medicine, Buffalo, New York.
authors.forename: Mandy
authors.initials: M
authors.lastname: Ma
authors.affiliation: Children's Hospital Boston, Boston, Massachusetts.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Barry
authors.affiliation: Department of Pediatrics, Division of Genetic Medicine, University of Washington, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Ghayda M
authors.initials: GM
authors.lastname: Mirzaa
authors.affiliation: Department of Pediatrics, Division of Genetic Medicine, University of Washington, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.affiliation: Genetics and Genomics Medicine, UCL-Institute of Child Health, London, United Kingdom.|North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Scott
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Trump
authors.affiliation: Developmental Neurosciences, UCL-Institute of Child Health, London, United Kingdom.|Department of Neurology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, New York.|Departments of Pediatrics and Biomedical Genetics, Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Paciorkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D005190:Family; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D013577:Syndrome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins
keywords: 14q12; FOXG1; familial recurrence; gonadal mosaicism