A novel heterozygous missense mutation 377T > C (V126A) of TGIF gene in a family segregated with holoprosencephaly and moyamoya disease.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, Republic of China. mchen_cch@yahoo.com
Ming
M
Chen
Shou-Jen
SJ
Kuo
Chin-San
CS
Liu
Wei-Liang
WL
Chen
Tsang-Ming
TM
Ko
Tze-Ho
TH
Chen
Shun-Ping
SP
Chang
Chien-Hao
CH
Huang
Yih-Yuan
YY
Chang
Bao-Tyan
BT
Wang
D000328:Adult; D001483:Base Sequence; D005260:Female; D005801:Genes, Homeobox; D006579:Heterozygote; D016142:Holoprosencephaly / Q000175:diagnosis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008969:Molecular Sequence Data; D009072:Moyamoya Disease / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics*; D013624:Taiwan; D016216:Ultrasonography, Prenatal
D018398:Homeodomain Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human