UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis
| Autor: | Hoi Soo Yoon, Ho Joon Im, Ki Woong Sung, Hyo Seop Ahn, Hyun Sook Chi, Ji Yoon Kim, Sun-Hee Kim, Hee Young Shin, Seung-Tae Lee, Keon Hee Yoo, Chan Jeoung Park, Ji Sook Shin, Young Tak Lim, Jong Jin Seo, Hee Jin Kim, Keun Wook Bae, Hae Sun Chung, Hong Hoe Koo, Hyoung Jin Kang, Ki O. Lee |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Haematologica. 95:622-626 |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Background Familial hemophagocytic lymphohistiocytosis is a fatal disease characterized by immune dysregulation from defective function of cytotoxic lymphocytes. Three causative genes have been identified for this autosomal recessive disorder ( PRF1 , UNC13D , and STX11 ). We investigated the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. Design and Methods Pediatric patients who fulfilled the HLH-2004 criteria were recruited from the Korean Registry for Histiocytosis. Molecular genetic studies were performed on the patients’ DNA samples by direct sequencing of all coding exons and flanking sequences of PRF1 , UNC13D , and STX11 . Results Forty patients were studied and familial hemophagocytic lymphohistiocytosis mutations were identified in nine; eight patients had UNC13D mutations (89%) and one had a mutation in PRF1 . No patient had a STX11 mutation. Notably, four patients had only one UNC13D mutant allele, suggesting that the other mutation was missed by conventional direct sequencing. All UNC13D mutations were deleterious in nature. One known splicing mutation, c.754-1G>C, was recurrent, accounting for 58% of all the mutant alleles (7/12). Five UNC13D mutations were novel (p.Gln98X, p.Glu565SerfsX7, c.1993-2A>G, c.2367+1G>A, and c.2954+5G>A). The one patient with PRF1 mutation was homozygous for a frameshift mutation (p.Leu364GlufsX93), which was previously reported to be the most frequent PRF1 mutation in Japan. Conclusions This is the first investigation on the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. The data showed that UNC13D is the predominant causative gene in the Korean population. The identification of mutations missed by conventional sequencing would better delineate the mutation spectrum and help to establish the optimal molecular diagnostic strategy for familial hemophagocytic lymphohistiocytosis in Korea, which might need an RNA-based screening strategy. |
| Databáze: | OpenAIRE |
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