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Familial recurrences of FOXG1 ‐related disorder: Evidence for mosaicism
Author(s) -
McMahon Kelly Q.,
Papandreou Apostolos,
Ma Mandy,
Barry Brenda J.,
Mirzaa Ghayda M.,
Dobyns William B.,
Scott Richard H.,
Trump Natalie,
Kurian Manju A.,
Paciorkowski Alex R.
Publication year - 2015
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37353
Subject(s) - germline mosaicism , microcephaly , genetics , corpus callosum , germline , biology , gene , neuroscience
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. © 2015 Wiley Periodicals, Inc.