Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2. Am J Med Genet A 2011 Jul;155A(7):1574-80
Date
06/04/2011Pubmed ID
21638761Pubmed Central ID
PMC3121908DOI
10.1002/ajmg.a.34029Scopus ID
2-s2.0-79959496472 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Rhombencephalosynapsis (RES) is a rare congenital brain malformation typically identified by magnetic resonance imaging and characterized by fusion of the cerebellar hemispheres and dentate nuclei and vermian agenesis or hypogenesis. Although RES is frequently found in conjunction with other brain malformations and/or congenital anomalies, no specific molecular etiology has been discovered to date and no animal models exist. We identified two half sisters with alobar or semi-lobar holoprosencephaly (HPE) and partial RES, suggesting that genes linked to HPE may also contribute to RES. A deletion of seven base pairs in exon one of the ZIC2 gene (c.392_98del7) was identified in each of the two half sisters with HPE and partial RES. To identify genetic causes of RES and to assess whether genes identified in HPE have a role in RES, we tested 11 additional individuals with RES by high-resolution chromosome analysis, chromosomal microarray analysis, and sequencing of four HPE genes. No mutations in ZIC2 or in other genes that cause HPE were identified, suggesting that mutation of ZIC2 is a rare cause of, or contributor to, RES associated with HPE. In addition, an individual with a complex rearrangement of chromosome 22q13.3 and RES was identified, suggesting the presence of a dosage-sensitive gene that may contribute to RES in this region.
Author List
Ramocki MB, Scaglia F, Stankiewicz P, Belmont JW, Jones JY, Clark GDAuthor
Test W. User test user title in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentChild
Child, Preschool
Chromosome Banding
Comparative Genomic Hybridization
Female
Holoprosencephaly
Humans
Infant
Male
Mutation
Nuclear Proteins
Rhombencephalon
Siblings
Transcription Factors