TGIF Mutations in Human Holoprosencephaly: Correlation between Genotype and Phenotype

摘要: Holoprosencephaly (HPE), which results from failed or incomplete midline forebrain division early in gestation, is the most common malformation. The etiology of HPE complex and multifactorial. To date, at least 12 HPE-associated genes have been identified, including TGIF (transforming growth factor beta-induced factor), located on chromosome 18p11.3. encodes a transcriptional repressor retinoid responses involved TGF-β signaling regulation, Nodal signaling. mutations are reported approximately 1–2% patients with non-syndromic, non-chromosomal HPE. We combined data our comprehensive studies literature search for all individuals evidence affecting order to establish genotypic phenotypic range. describe 2 groups patients: 34 intragenic 21 deletions TGIF. These individuals, were ascertained research group, collaboration other centers, through search, include 38 probands 17 mutation-positive relatives. majority occur homeodomain. Patients TGIFrecapitulate entire spectrum observed non-chromosomal, non-syndromic identified statistically significant difference between respect inheritance, as more likely be de novo comparison (χ2(2) = 6.97, ppermutated 0.0356). In addition, also found commonly present manifestations beyond craniofacial neuroanatomical features associated (p 0.0030). findings highlight differences versus TGIF, draw attention homeodomain region, appears particularly relevant may useful genetic counseling affected patients.