FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction.
FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction.
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DOI：
10.1097/mpa.0000000000000529
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发表时间：
2016-07
期刊：
影响因子：
2.9
通讯作者：
Shimamura A
中科院分区：
文献类型：
--
作者：
Seo A;Walsh T;Lee MK;Ho PA;Hsu EK;Sidbury R;King MC;Shimamura A
迄今为止，很少有关于胰腺外分泌功能障碍的遗传原因的报道。我们确定了一个家庭的多个受影响的成员表现出胰腺外分泌功能障碍。其他相关特征包括面部皮疹、毛发稀疏、多汗和四肢肿胀。这些临床特征的传播模式与常染色体显性遗传模式一致。这两个先证者的兄弟姐妹在生命早期也有短暂的肝转氨酶升高伴肝脂肪变性。本研究确定了该家族胰腺外分泌功能障碍的遗传原因。进行全外显子组测序以确定胰腺外分泌功能障碍的遗传原因。基因FAM111B（c.1261_1263delAAG，p.Lys421del）中的杂合种系框内缺失与表型共分离：该变体存在于所有受影响的亲属中，而在所有未受影响的亲属中不存在。该变体也不存在于公共控制序列数据库中。我们的研究结果表明FAM 111 B与常染色体显性遗传的外分泌胰腺功能障碍有关。
Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities. The transmission pattern of these clinical features was consistent with an autosomal dominant mode of inheritance. The two proband siblings also had transient elevated liver transaminases with hepatic steatosis early in life. This study identifies the genetic cause of exocrine pancreatic dysfunction in this family. Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction. A heterozygous germline in-frame deletion in the gene FAM111B (c.1261_1263delAAG, p.Lys421del) co-segregated with the phenotype: the variant was present in all affected relatives genotyped and absent in all unaffected relatives genotyped. The variant is also absent from public control sequence databases. Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction.