Sensitive and efficient detection of @entity996 gene mutations enhances care for families with XXXX .

@entity1 @entity996 @entity5 @entity995
Timely molecular diagnosis of @entity996 mutations enables earlier treatment, lower risk, and better health outcomes for @entity1 with @entity995 ; empowers families to make informed family-planning decisions; and costs less than conventional surveillance. However, complexity has hindered clinical implementation of molecular diagnosis. The majority of @entity996 mutations are unique and distributed throughout the @entity996 gene, with no real hot spots. We devised a sensitive and efficient strategy to identify @entity996 mutations that combines quantitative multiplex polymerase chain reaction (QM-PCR), double-exon sequencing, and promoter-targeted methylation-sensitive PCR. Optimization of test order by stochastic dynamic programming and the development of allele-specific PCR for four recurrent point mutations decreased the estimated turnaround time to <3 wk and decreased direct costs by one-third. The multistep method reported here detected 89% (199/224) of mutations in bilaterally affected probands and both mutant alleles in 84% (112/134) of @entity5 from unilaterally affected probands. For 23 of 27 exons and the promoter region, QM-PCR was a highly accurate measure of deletions and insertions (accuracy 95%). By revealing those family members who did not carry the mutation found in the related proband, molecular analysis enabled 97 at-risk @entity1 from 20 representative families to avoid 313 surveillance examinations under anesthetic and 852 clinic visits. The average savings in direct costs from clinical examinations avoided by @entity1 in these families substantially exceeded the cost of molecular testing. Moreover, health care savings continue to accrue, as @entity1 in succeeding generations avoid unnecessary repeated anaesthetics and examinations.
