title: Molecular diagnosis of a novel heterozygous 268C-->T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis.
abstract: We report the sonographic diagnosis and molecular analysis of holoprosencephaly (HPE) and premaxillary agenesis in a second-trimester fetus with a 46,XY karyotype. Mutational sequence analyses for the entire coding region and exon-intron boundaries of SHH, ZIC2, SIX3 and TGIF genes identified a novel heterozygous missense TGIF mutation 268C-->T (CGC-->TGC change) that predicts an Arg90Cys substitution in the homeodomain region of TGIF. The proband's parents did not carry the mutation. The present case is an example of the heterogeneous entity of the HPE spectrum and demonstrates that adjunctive molecular analyses of distinct human genes for HPE can reassure genetic counselling by elucidating the genetic pathogenesis, especially in cytogenetically normal fetuses affected with HPE.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China. cpc_mmh@yahoo.com
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.forename: Shin-Hua
authors.initials: SH
authors.lastname: Du
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005865:Gestational Age; D006579:Heterozygote; D016142:Holoprosencephaly / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008437:Maxilla / Q000002:abnormalities*; D009154:Mutation; D020125:Mutation, Missense; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human