Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort.
Schizencephaly is a malformation of cortical development characterized by gray matter-lined clefts in the cerebral cortex and a range of neurological presentations. In some cases, there are features of septo-optic dysplasia concurrently with schizencephaly. The etiologies of both schizencephaly and septo-optic dysplasia are thought to be heterogeneous, but there is evidence that at least some cases have genetic origin. We hypothesized that these disorders may be caused by mutations in three candidate genes: LHX2, a gene with an important cortical patterning role, and HESX1 and SOX2, genes that have been associated with septo-optic dysplasia. We sequenced a large cohort of patients with schizencephaly, some with features of septo-optic dysplasia, for mutations in these genes. No pathogenic mutations were observed, suggesting that other genes or non-genetic factors influencing genes critical to brain development must be responsible for schizencephaly.
Department of Neurology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cecilia
C
Mellado
Annapurna
A
Poduri
Danielle
D
Gleason
Princess C
PC
Elhosary
Brenda J
BJ
Barry
Jennifer N
JN
Partlow
Bernard S
BS
Chang
Gary M
GM
Shaw
A James
AJ
Barkovich
Christopher A
CA
Walsh
D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D060850:LIM-Homeodomain Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D025962:Septo-Optic Dysplasia / Q000150:complications / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors