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Whole‐exome sequencing of a unique brain malformation with periventricular heterotopia, cingulate polymicrogyria and midbrain tectal hyperplasia
Author(s) -
Okumura Akihisa,
Hayashi Masaharu,
Shimojima Keiko,
Ikeno Mitsuru,
Uchida Tomohisa,
Takanashi Junichi,
Okamoto Nobuhiko,
Hisata Ken,
Shoji Hiromichi,
Saito Akira,
Furukawa Toru,
Kishida Tetsuko,
Shimizu Toshiaki,
Yamamoto Toshiyuki
Publication year - 2013
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12007
Subject(s) - polymicrogyria , pathology , white matter , anatomy , exome sequencing , heterotopia (medicine) , midbrain , biology , medicine , neuroscience , magnetic resonance imaging , epilepsy , genetics , central nervous system , mutation , radiology , gene
We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR ‐based sequencing. Whole‐exome sequencing confirmed the presence of novel gene variants for filamin B ( FLNB ), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X ‐linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.