Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes
Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes
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DOI：
10.1111/j.1399-0004.2008.01026.x
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发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Sistermans, E. A.
中科院分区：
文献类型：
--
作者：
Menko, F. H.;Kneepkens, C. M. F.;Sistermans, E. A.
小儿息肉病是一种罕见的疾病，具有严重的胃肠道症状和严重的临床病程。最近，在4例小儿息肉病患者中发现了涉及PTEN和BMPR1A基因的10q23微缺失。据推测，两种基因缺失的联合和协同效应可以解释这种情况。然而，随后发现了一名10q23缺失较大的患者，其中包括相同的基因，但临床表型较轻。在这里，我们提出了另外四例涉及PTEN和BMPR1A基因的10q23微缺失的患者。使用单核苷酸多态性阵列分析分析缺失的大小。所有患者均有大头畸形、畸形、发育迟缓和先天性异常。一名患者患上了结肠直肠癌。然而，只有1例在2岁前发病，症状严重需要结肠切除术。在发病年龄或胃肠道症状的严重程度与缺失的大小之间没有发现明确的相关性。我们得出结论，涉及PTEN和BMPR1A基因的10q23微缺失患者具有可变的临床表型，这不能仅仅通过缺失大小来解释。其表型并不局限于严重的小儿息肉病，还包括儿童期发病的大头畸形、发育迟缓、轻度胃肠道症状和可能的早发性结直肠癌。
Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic effect of the deletion of both genes would explain the condition. Subsequently, however, a patient with a larger 10q23 deletion including the same genes but with a mild clinical phenotype was identified. Here, we present four additional patients with 10q23 microdeletions involving the PTEN and BMPR1A genes. The sizes of the deletions were analyzed using single nucleotide polymorphism array analysis. All patients had macrocephaly, dysmorphic features, retardation and congenital abnormalities. One patient developed colorectal cancer. However, only one case had disease onset before 2 years of age and severe symptoms requiring colectomy. No clear correlation was found between ages at onset or severity of gastrointestinal symptoms and the sizes of the deletions. We conclude that patients with 10q23 microdeletions involving the PTEN and BMPR1A genes have variable clinical phenotypes, which cannot be explained merely by the deletion sizes. The phenotypes are not restricted to severe infantile juvenile polyposis but include childhood-onset cases with macrocephaly, retardation, mild gastrointestinal symptoms and possibly early-onset colorectal cancer.