Eun-Sook Kim

SLC25A4 and C10ORF2 Mutations in Autosomal Dominant Progressive External Ophthalmoplegia.

Background and Purpose Progressive external ophthalmoplegia (PEO) with Mendelian inheritance is a heterogeneous group of diseases associated with multiple deletions of mitochondrial DNA (mtDNA), which results from the disturbed replication and maintenance of mtDNA secondary to the mutations of nuclear genes including POLG, SLC25A4, C10ORF2, POLG2, OPA1, and RRM2B. The aim of this study was to identify the genetic defects underlying the pathology and clinical features in two Korean kindreds with autosomal dominant PEO. Methods Two pathologically proven PEO patients with a clear autosomal dominant pattern of inheritance were selected. To exclude a large-scale rearrangement, a long-range polymerase chain reaction (PCR) was performed using DNA extracted from biopsied muscle tissue taken from each patient. All coding regions and exon-intron boundaries of POLG, SLC25A4, C10ORF2, and POLG2 were amplified by PCR and directly sequenced. Results One patient showed multiple deletions of mtDNA on long-range PCR analysis, and two known heterozygous missense mutations in SLC25A4 (p.Asp104Gly) and C10ORF2 (p.Glu479Lys) were identified in each patient. The p.Asp104Gly mutation in SLC25A4 was identified in the patient with an early onset, slowly progressive, pure PEO phenotype, while the p.Glu479Lys mutation in C10ORF2 was identified in the other patient, with a late-onset disease and PEO plus phenotype. Conclusions Two mutations affecting nuclear genes were identified in Korean patients with autosomal dominant PEO. Further studies are necessary to identify the clear pathogenetic mechanisms and establish genotype-phenotype correlations in autosomal dominant PEO.

Labialization in Nuuchahnulth

In this article we examine the phonetic properties of labialization in Nuuchahnulth, a Southern Wakashan language spoken on Vancouver Island. Given the moribund status of this language, we make use of available archival materials from the early twentieth century along with more recent recordings in order to ascertain the exact nature of the process. Early work on this language was conducted by Edward Sapir, who transcribed data in a more or less phonetic form. A second goal of our paper is to test the accuracy of Sapirs transcriptions. Finally, we examine the characteristics of Nuuchahnulth labialization which mark it as an important typological phenomenon.