SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype
JOURNAL OF MEDICAL GENETICS
Authors: Spurlock, G.; Bennett, E.; Chuzhanova, N.; Thomas, N.; Jim, H-Ping; Side, L.; Davies, S.; Haan, E.; Kerr, B.; Huson, S. M.; Upadhyaya, M.
Objective: Mutations of the SPRED1 gene, one of a family of Sprouty (Spry)/Spred proteins known to "downregulate'' mitogen activated protein kinase (MAPK) signalling, have been identified in patients with a mild neurofibromatosis type 1 (NF1) phenotype with pigmentary changes but no neurofibromas (Legius syndrome). To ascertain the frequency of SPRED1 mutations as a cause of this phenotype and to investigate whether other SPRED/SPRY genes may be causal, a panel of unrelated mild NF1 patients were screened for mutations of the SPRED1-3 and the SPRY1-4 genes. Methods: 85 patients with a mild NF1 phenotype were screened for SPRED1 mutations. 44 patients negative for both NF1 and SPRED1 mutations were then screened for SPRED2-3 and SPRY1-4 mutations. Complexity analysis was applied to analyse the flanking sequences surrounding the identified SPRED1 mutations for the presence of direct and inverted repeats or symmetric sequence elements in order to infer probable mutational mechanism. Results: SPRED1 mutations were identified in 6 cases; 5 were novel and included 3 nonsense (R16X, E73X, R262X), 2 frameshift (c. 1048_c1049 delGG, c. 149_1152del 4 bp), and a single missense mutation (V44D). Short direct or inverted repeats detected immediately adjacent to some SPRED1 mutations may have led to the formation of the microdeletions and base pair substitutions. Discussion: The identification of SPRED1 gene mutation in NF1-like patients has major implications for counselling NF1 families.
A Study on the Expression of SPRED1 and PBRM1 (Baf180) and their Clinical Significances in Patients with Gastric Cancer
Authors: Liu, Weirong; Fang, Shouguo; Zuo, Guojin
Background: To evaluate SPRED1 and PBRMl expression in patients with gastric cancer and determine the biological relationships of SPRED1 and PBRM1 with the occurrence and development of gastric cancer. Methods: Tissue specimens of patients with gastric cancer at Jingzhou First People's Hospital were gathered from April 2016 to August 2018. SPRED1 and PBRMl (Baf180) protein expression levels were detected in the excised cancerous tissues and normal tissues (control group) of 80 patients with gastric cancer by immunohistochemical methods. Results: The positive rates of SPRED1 and PBRMl protein expression in gastric cancer tissues were 55% and 75%, respectively. The positive rates of SPRED1 and PBRMl protein expression in the normal tissues without cancer were 84.6% and 92.3%, respectively. The expression in gastric cancer tissues was significantly lower than that of the control group (p < 0.05). Positive SPRED1 and PBRMl protein expression was related to histological type, depth of infiltration, presence of lymphatic metastasis, pathological grade, and clinical TNM phase (p < 0.05). SPRED1 expression and PBRMl expression were positively correlated. Conclusions: The expression of SPRED1 and PBRMl in gastric cancer tissues is low, unrelated to age and declines with increasing pathological grade and clinical phase of the gastric cancer tissues. SPRED1 and PBRMl expression may be related to the biological behavior of tumors, and the two may have a synergistic effect.