OBJECTIVES: To identify whether any mutations of candidate genes including SHH, 
ZIC2, SIX3, and TGIF exist in a Taiwanese family segregated with 
holoprosencephaly (HPE) and moyamoya disease.
METHODS: Genotypes of the candidate genes SHH, ZIC2, SIX3, and TGIF were 
determined in the family members who were available for analysis by sequencing. 
In addition, genomic regions of another 50 unrelated Taiwanese (100 chromosomes) 
were studied to verify whether the nucleotide changes we found were mutations or 
polymorphisms.
RESULTS: A novel missense mutation 377T > C and two polymorphisms (420A > G and 
487C > T) in the TGIF gene were identified. No mutations in SHH, ZIC2 and SIX3 
were found. The mother of the three HPE fetuses was found to be afflicted with 
moyamoya disease. A brief review of the mutations as well as polymorphisms 
reported in the TGIF gene up to 2005 is given.
CONCLUSION: Molecular diagnosis can help genetic counseling in HPE, which is a 
heterogeneous disorder with its phenotypic and genotypic spectrum highly widened 
and variable. The possible association between TGIF mutation and moyamoya 
disease noted in our study also appeared to be novel.