Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome).

摘要: Pitt-Hopkins syndrome is a rarely reported of so-far-unknown etiology characterized by mental retardation, wide mouth, and intermittent hyperventilation. By molecular karyotyping with GeneChip Human Mapping 100K SNP arrays, we detected 1.2-Mb deletion on 18q21.2 in one patient. Sequencing the TCF4 transcription factor gene, which contained region, 30 patients significant phenotypic overlap revealed heterozygous stop, splice, missense mutations five further severe retardation remarkable facial resemblance. Thus, establish as distinct but probably heterogeneous entity caused autosomal dominant de novo TCF4. Because its overlap, evolves an important differential diagnosis to Angelman Rett syndromes. Both null impaired interaction ASCL1 from PHOX-RET pathway transactivating E box-containing reporter construct; therefore, hyperventilation Hirschsprung disease might be explained altered development noradrenergic derivatives.