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Am J Med Genet A. 2015 Dec;167A(12):3096-102. doi: 10.1002/ajmg.a.37353. Epub 2015 Sep 14.

Familial recurrences of FOXG1-related disorder: Evidence for mosaicism.

Author information

1
Department of Neurology, University of Rochester Medical Center, Rochester, New York.
2
Developmental Neurosciences, UCL-Institute of Child Health, London, United Kingdom.
3
Department of Neurology, Great Ormond Street Hospital, London, United Kingdom.
4
Genetics and Genomics Medicine, UCL-Institute of Child Health, London, United Kingdom.
5
University of Buffalo School of Medicine, Buffalo, New York.
6
Children's Hospital Boston, Boston, Massachusetts.
7
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
8
North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, United Kingdom.
9
Departments of Pediatrics and Biomedical Genetics, Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York.

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.

KEYWORDS:

14q12; FOXG1; familial recurrence; gonadal mosaicism

PMID:
26364767
PMCID:
PMC4715619
DOI:
10.1002/ajmg.a.37353
[Indexed for MEDLINE]
Free PMC Article

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