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BRAT1 ‐associated neurodegeneration: Intra‐familial phenotypic differences in siblings
Author(s) -
Smith Nicholas J.,
Lipsett Jill,
Dibbens Leanne M.,
Heron Sarah E.
Publication year - 2016
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.37853
Subject(s) - microcephaly , neurodegeneration , phenotype , hypertonia , disease , sibling , epilepsy , missense mutation , medicine , compound heterozygosity , genetics , pediatrics , biology , neuroscience , pathology , psychology , gene , developmental psychology
Recessive mutations in BRAT1 cause lethal neonatal rigidity and multifocal seizure syndrome, a phenotype characterized by neonatal microcephaly, hypertonia, and refractory epilepsy with premature death by age 2 years. Recently, attenuated disease variants have been described, suggesting that a wider clinical spectrum of BRAT1 ‐associated neurodegeneration exists than was previously thought. Here, we report two affected siblings with compound heterozygous truncating mutations in BRAT1 and intra‐familial phenotypic heterogeneity, with a less severe disease course in the female sibling. This phenotypic variability should be taken into account when treating patients with BRAT1 ‐associated neurodegenerative disease. Mildly affected individuals with BRAT1 mutations show that BRAT1 must be considered as a cause in childhood refractory epilepsy and microcephaly with survival beyond infancy. © 2016 Wiley Periodicals, Inc.