Genes, Vol. 12, Pages 1595: Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology

Genes, Vol. 12, Pages 1595: Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology Genes doi: 10.3390/genes12101595 Authors: Erwin Brosens Rutger W. W. Brouwer Hannie Douben Yolande van Bever Alice S. Brooks Rene M. H. Wijnen Wilfred F. J. van IJcken Dick Tibboel Robbert J. Rottier Annelies de Klein Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substan...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research