Laryngeal paralysis is a frequent cause of stridor and airway obstruction in infants, often requiring tracheostomy or other surgical procedures to provide an adequate airway. Hereditary forms of laryngeal paralysis have been described, indicating that genetic factors may be a primary cause of certain cases. The long term objective of this study is to identify the role of genetic mechanisms in laryngeal paralysis. The hypothesis to be tested is that genetic mutations cause familial laryngeal abductor paralysis (FLAP).
The specific aims of this project are: 1) To identify genetic loci linked to FLAP- Genetic linkage analysis of families in which FLAP segregates is accomplished by PCR-based screening with a short tandem repeat polymorphism (STRP) panel that covers the entire human genome. This is confirmed by statistical analysis using the LOD score method and the computer programs, SLINK, LINKAGE 5.1 and HOMOG. 2) To identify candidate genes in the chromosomal region(s) linked to FLAP- known and predicted genes are identified within FLAP genetic region(s) by sequence analysis of data from the Human Genome Project. Positional candidate genes are prioritized for mutation screening according to gene expression and function that appear consistent with the FLAP phenotype and its possible disease mechanisms. 3) To identify FLAP-causing genes- Single strand conformation polymorphism (SSCP) gel analysis and direct sequencing are used to screen genomic DNA for FLAP-causing mutations. Detected mutations are further analyzed by population screening, computer analysis of the mutated sequence, and tissue in situ hybridization studies to determine the likelihood that a specific genetic mutation causes FLAP.
