Genetic studies of structural anomalies in humans help to better understand the underlying basis for normal and abnormal embryological development. We have studied the most common brain anomaly in humans, holoprosencephaly (HPE), a structural defect of the developing forebrain and midface. HPE is a genetically heterogeneous disorder associated with various chromosomal anomalies. Recently, mutations in the human Sonic Hedgehog (SHH)gene , ZIC2 gene, and SIX3 gene were shown to cause familial and sporadic forms of HPE. Furthermore, anomalies in the cholesterol biosynthesis were found in a genetic syndrome associated with HPE. Thus, other yet unidentified HPE causing genes are postulated to be part of the SHH signaling pathway or are involved in the cholesterol biosynthesis. Other candidate genes which we are analyzing include the human OEP analogs CRYPTIC and CRYPTO, DKK1, and GLI1 and GLI2. - Brain Disorders Decade of the Brain Dental/Oral Disease Genetics Human Genome Research Mental Retardation Pediatric Research - Human Subjects

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Intramural Research (Z01)
Project #
Application #
Study Section
Molecular Genetics B Study Section (MGB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Human Genome Research
United States
Zip Code
Arcos-Burgos, M; Castellanos, F X; Konecki, D et al. (2004) Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate. Mol Psychiatry 9:252-9
Schimmenti, Lisa A; de la Cruz, June; Lewis, Richard Alan et al. (2003) Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia. Am J Med Genet A 116A:215-21
Schell-Apacik, Can; Rivero, Mariel; Knepper, Jessica L et al. (2003) SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. Hum Genet 113:170-7
Edison, Robin; Muenke, Maximilian (2003) The interplay of genetic and environmental factors in craniofacial morphogenesis: holoprosencephaly and the role of cholesterol. Congenit Anom (Kyoto) 43:1-21
Roessler, Erich; Muenke, Maximilian (2003) How a Hedgehog might see holoprosencephaly. Hum Mol Genet 12 Spec No 1:R15-25
de la Cruz, June M; Bamford, Richard N; Burdine, Rebecca D et al. (2002) A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. Hum Genet 110:422-8
Ming, Jeffrey E; Muenke, Maximilian (2002) Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 71:1017-32
Orioli, Ieda M; Vieira, Alexandre R; Castilla, Eduardo E et al. (2002) Mutational analysis of the Sonic Hedgehog gene in 220 newborns with oral clefts in a South American (ECLAMC) population. Am J Med Genet 108:12-5
Davis, Richard L; Shrimpton, Antony E; Carrell, Robin W et al. (2002) Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet 359:2242-7
Lacbawan, Felicitas L; Muenke, Maximilian (2002) Central nervous system embryogenesis and its failures. Pediatr Dev Pathol 5:425-47

Showing the most recent 10 out of 17 publications