The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletions

• Published in: Human genetics 2011-12, Vol.130 (6), p.777-787
• Main Authors: Hasi, Minire, Soileau, Bridgette, Sebold, Courtney, Hill, Annice, Hale, Daniel E., O’Donnell, Louise, Cody, Jannine D.
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Autism; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Child; chromosome 18; Chromosome Aberrations; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 18; Classical genetics, quantitative genetics, hybrids; Cognitive ability; Cohort Studies; Corpus callosum; Data processing; Facies; Family; Female; Finger; Fundamental and applied biological sciences. Psychology; Gene deletion; Gene Function; Genes; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Genotype & phenotype; Hemizygosity; Hemizygote; Human; Human Genetics; Humans; Hyperventilation - genetics; Intellectual disabilities; Intellectual Disability - genetics; Male; Medical records; Metabolic Diseases; Molecular Medicine; Mutation; Neck; Nipples; Original Investigation; Penis; Phenotype; Prognosis; Research centers; Sacrum; Schizophrenia; Surveys; Syndrome; Transcription Factor 4; Transcription factors; Transcription Factors - genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-011-1020-y

The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 ( TCF4 + / − ); nine had deletions that did not include TCF4 ( TCF4 + / + ); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants’ medical records, survey responses, and in-person evaluations. Features unique to the TCF4 + / − individuals included abnormal corpus callosum, short neck, small penis, accessory and wide-spaced nipples, broad or clubbed fingers, and sacral dimple. The developmental data revealed that TCF4 + / + individuals were only moderately developmentally delayed while TCF4 + / − individuals failed to reach developmental milestones beyond those typically acquired by 12 months of age. TCF4 hemizygosity also conferred an increased risk of early death principally due to aspiration-related complications. Hemizygosity for TCF4 confers a significant impact primarily with regard to cognitive and motor development, resulting in a very different prognosis for individuals hemizygous for TCF4 when compared to individuals hemizygous for other regions of distal 18q.