A Japanese family with Alport syndrome associated with esophageal leiomyomatosis: genetic analysis of COL4A5 to COL4A6 and immunostaining for type IV collagen subtypes.
A Japanese family with Alport syndrome associated with esophageal leiomyomatosis: genetic analysis of COL4A5 to COL4A6 and immunostaining for type IV collagen subtypes.
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DOI：
10.5414/cnp64144
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发表时间：
2005-08
影响因子：
1.1
通讯作者：
K. Sugimoto;H. Yanagida;K. Yagi;H. Kuwajima;M. Okada;T. Takemura
中科院分区：
文献类型：
--
作者：
K. Sugimoto;H. Yanagida;K. Yagi;H. Kuwajima;M. Okada;T. Takemura
背景在一些家系中，X连锁Alport综合征(AS)与弥漫性子宫肌瘤病相关。我们描述了一个日本家系的临床、病理和分子遗传学研究结果，该家系的遗传方式与子宫肌瘤病相关。强直性脊柱炎患者为一名一岁男童，因子宫肌瘤病引起的食道狭窄而导致反复吸入性肺炎。诊断是通过电子显微镜结合IV型胶原链亚型染色在肾活检标本确认的。他的母亲表现为食道平滑肌瘤病并为AS杂合子，在皮肤活检标本中显示沿表皮基底膜的α5(IV)胶原链不连续染色。对这名男孩的遗传分析显示，COL4A6的前两个外显子缺失，COL4A5的5‘端缺失。尽管使用了环孢素A，但男孩仍有大量蛋白尿，尽管肾功能在其他方面仍保持正常。结论在婴儿期诊断为强直性脊柱炎患者极为罕见。临床表现包括肉眼血尿、白内障和由COL4A5至COL4A6大片段缺失引起的子宫肌瘤病，导致AS的早期表现。
BACKGROUND In some families, X-linked Alport syndrome (AS) is associated with diffuse leiomyomatosis. We describe clinical, pathologic and molecular-genetic findings in a Japanese family with this inheritance mode of AS in association with leiomyomatosis. PATIENT AS was diagnosed in a one-year-old boy with recurrent aspiration pneumonia caused by esophageal stenosis from leiomyomatosis. Diagnosis was confirmed by electron microscopy coupled with type IV collagen chain subtype staining in a renal biopsy specimen. His mother, who exhibited esophageal leiomyomatosis and is heterozygous for AS, showed a discontinuous staining pattern for collagen alpha5(IV) chain along the epidermal basement membrane in a skin biopsy specimen. Genetic analysis in the boy revealed the deletion of the first two exons of COL4A6 together with deletion of the 5' end of COL4A5. Despite administration of cyclosporin A, massive proteinuria has persisted in the boy, although renal function otherwise remains normal. CONCLUSION Identification of an AS patient during infancy is extremely rare. Clinical manifestations, including macroscopic hematuria, cataracts and leiomyomatosis caused by the large deletion involving COL4A5 to COL4A6, led to early presentation with AS.