A new lysozyme tyr54asn mutation causing amyloidosis in a family of Swedish ancestry with gastrointestinal symptoms
A new lysozyme tyr54asn mutation causing amyloidosis in a family of Swedish ancestry with gastrointestinal symptoms
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DOI：
10.3109/13506129.2012.723074
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发表时间：
2012-12-01
影响因子：
5.5
通讯作者：
Connors, Lawreen H.
中科院分区：
文献类型：
--
作者：
Girnius, Saulius;Skinner, Martha;Connors, Lawreen H.
家族性淀粉样变性是一组遗传性疾病，导致错误折叠的淀粉样蛋白在各种组织中沉积，导致器官功能障碍。已知七种不同基因编码区的点突变会导致临床上意义重大的系统性淀粉样疾病。我们描述了一位61岁女性的溶菌酶基因外显子2的新突变与淀粉样变性(Alys)相关，她有7年的非血性、水样腹泻和体重减轻的病史。十二指肠和胃的活检组织中固有层和血管中的淀粉样沉积呈阳性。对溶菌酶基因的直接DNA测序显示，在54密码子的第一位有一个从T到A的单碱基核苷酸转换，导致成熟的溶菌酶蛋白(PTyr54Asn)中的Tyr被Asn取代。从脂肪组织样本中提取的淀粉样纤维的免疫印迹分析证实，溶菌酶是淀粉样蛋白。临床上，与这种溶菌酶突变相关的表型表现为慢性腹痛、腹泻、体重减轻、吸收不良和干燥综合征。没有其他Alys突变所报告的相关肾病。我们描述了一种新的突变型溶菌酶，表现为腹部不适、腹泻、体重减轻和干燥综合征。
Familial amyloidoses are a group of inherited disorders that cause deposition of misfolded amyloidogenic proteins in various tissues, resulting in organ dysfunction. Point mutations in the coding region of seven different genes are known to cause clinically significant systemic amyloid disease. We describe a new mutation in exon 2 of the lysozyme gene associated with amyloidosis (ALys) in a 61-year-old woman with a 7-year history of non-bloody, watery diarrhea, and weight loss. Biopsies of the duodenum and stomach were positive for amyloid deposits in the lamina propria and blood vessels. Direct DNA sequencing of the lysozyme gene revealed a single base nucleotide transversion from T to A at the first position of codon 54, resulting in replacement of Tyr by Asn in the mature lysozyme protein (pTyr54Asn). Immunoblot analysis of amyloid fibrils extracted from a fat tissue sample confirmed lysozyme as the amyloid protein. Clinically, the phenotype associated with this lysozyme mutation featured chronic abdominal pain, diarrhea, weight loss, malabsorption, and sicca syndrome. There was no associated nephropathy as has been reported for other ALys mutations. We describe a new mutant lysozyme that presents with abdominal discomfort, diarrhea, weight loss, and sicca syndrome.