Analysis Of SDHD And SDHB Gene Mutations In Paragangliomas

Objective: To find out the prevalence of SDHD and SDHB mutations in patients with paraganglioma from china and to find out whether there is any difference with respect to the data published in other populations. The study is designed to provide the basis for further study of molecular diagnosis and molecular genetics of paraganglioma and faciliate early detection and early treatment for paragangliomas. Methods: Eight sporadic PGL patients and one familial PGL patient with complete clinical and pathological data were investigated. All of them were preliminarily diagnosed at Tianjin Medical University Cancer Hospital from 2006 April to 2007 December. We also have 18 blood samples of normal control and bloods of four members of the familial case investigated. Peripheral venous bloods were gained and genomic DNA was extracted by TKM method. Each amplification fragment of SDHD and SDHB exons gained through PCR are sequenced directly after purification. Finaly the results of sequencing are compaired with standard sequence published in the NCBI net using the software of BLAST. Results:1. The familial case studied here carried a heterozygotic missense mutations in SDHD. The mutation was W43X, located in SDHD-exon 2 and changing the codon presenting tryptophane to stop coden. The patient's father, uncle and her son shared the same mutation with her. None of the 8 sporadic cases studied carried mutations in SDHD.2. Two sporadic cases studied carried samesense germline mutations in SDHB-exon 1 which located in the 18th base pair, C substituted by A, making the 6th codon change from GCC to GCA. However both GCC and GCA encode for alamine. Both of the two patients had malignant leisions and an early onset that was 17-year old and 30-year old respectively. SDHB gene mutation was not found in the familial case studied.Conclusions:1. The familial case studied carried mutation in SDHD gene, which suggested SDHD mutation may be one of the molecular basis of Chinese paraganglioma genesis. Genetic testing of familial cases can help to reveal mutation carriers and faciliate early detection and early treament.2. In this study SDHD mutations were not found in sporadic patients with single paraganglioma from china. SDHD gene prevalence is low in this group of patients.3. 25% sporadic paraganglioma patients studied carried samesense mutation in SDHB-exon 1 A6A. The carriers all had pathologically maligmant lesions, which might suggest that single strand polymorphism may affect the phenotype of paraganglioma.4. SDHD and SDHB test is of significance to multicentric, early onset and pathologically malignant Chinese patients with paraganglioma.