Paragangliomas 1 with or without Sensorneural Hearing Loss
In 5 families with autosomal dominant hereditary paraganglioma (PGL1; 168000), Baysal et al. (2000) identified a C-to-T transition in the SDHD gene, resulting in a pro81-to-leu (P81L) substitution. The proline at position 81 is conserved in human, Bos taurus, Ascaris, and Caenorhabditis elegans.
Milunsky et al. (2001) found the pro81-to-leu mutation in 3 of 7 families with hereditary paragangliomas. Since this mutation results in the elimination of a normally occurring restriction endonuclease site (MspI), Milunsky et al. (2001) developed a restriction enzyme assay to screen for this mutation.
Badenhop et al. (2001) found the P81L mutation in an individual with sensorineural deafness in association with paragangliomas, as well as in 3 other family members who had only paragangliomas.
In an analysis of 23 families with paragangliomas-1, Astrom et al. (2003) identified the P81L mutation in 14 (approximately 61%). P81L had been implicated both as a founder and as a recurrent mutation among U.S. families (Baysal et al., 2002). Haplotype analyses of the 14 P81L carrier families indicated that 5 lacked the founder haplotype, suggesting independent origin.
Pheochromocytoma, Somatic
Gimm et al. (2000) found the P81L mutation in the heterozygous state as a somatic mutation in tumor tissue from a patient with sporadic (nonfamilial) pheochromocytoma (see 171300). Flanking markers also showed loss of heterozygosity.
