Localization of the gene for familial laryngeal abductor paralysis to chromosome 6q16.

Abstract

Vocal fold paralysis is a common cause of neonatal stridor. Although it is usually classified as idiopathic or iatrogenic in origin, a small subset of patients have a family history of this disorder, indicating a possible genetic cause. To identify the genetic locus of the gene that causes familial laryngeal abductor paralysis. A standard nonorganic protocol was used to extract DNA from whole-blood samples. The DNA samples were quantified by DNA fluorometry, and the concentration of all samples was standardized at 40 ng/microL. A pooled DNA strategy was used to facilitate rapid polymerase chain reaction screening of markers in the Weber v8.0 genome screening set. Polymerase chain reaction screening of individual DNA samples was performed using possible linked markers initially identified as having an allele that appeared with a higher incidence in the affected DNA pools. Statistical analysis of possible linkage was performed using the LINKAGE 5.1 set of linkage analysis computer programs. A family in which a form of familial laryngeal abductor paralysis segregates was ascertained. Whole blood samples were drawn from 40 participating individuals within this family after the subjects' fully informed consent was obtained. Initial screening of the pooled DNA specimens revealed a band pattern for D6S1021 on chromosome 6q16, indicating an allele with a higher incidence in the affected vs the nonaffected pool. Two-point analysis of individual allele patterns confirmed linkage to D6S1021 with an lod score of 3.86 (straight theta = 0.0) at a penetrance value of 0.8. Haplotype analysis with flanking markers defined a 5-centiray critical region between D6S283 and AFMA047YG1. An autosomal dominant form of familial laryngeal abductor paralysis is linked to a 5-centiray region on chromosome 6q16 surrounding D6S1021.