Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations
Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations
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DOI：
10.1038/jhg.2009.51
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发表时间：
2009-07
影响因子：
3.5
通讯作者：
R. Sasaki;Kayoko Saito;Yorikatsu Watanabe;Yoshinaga Takayama;K. Fujii;Kaori Agawa;T. Miyashita;T. Ando;T. Akizuki
中科院分区：
文献类型：
--
作者：
R. Sasaki;Kayoko Saito;Yorikatsu Watanabe;Yoshinaga Takayama;K. Fujii;Kaori Agawa;T. Miyashita;T. Ando;T. Akizuki
痣样基底细胞癌综合征（NBCCS）是一种罕见的常染色体显性遗传疾病，其特征是发育异常和易患癌症。两个无关的患者，21岁和16岁的男性，唇腭裂和多发性颌骨囊肿，诊断根据临床标准。为了证实NBCCS的诊断，我们对PTCH基因进行了分子遗传学分析。他们的PTCH基因进行了分析，直接测序的PCR产物从他们的DNA，和以前未报告的突变被确定。在PTCH基因的3325和3328之间的核苷酸位置处的杂合重复（c. 3325_3328dupGGCG）。它引起移码突变，导致PTCH蛋白的提前终止。PTCH基因内含子7中的点突变（G至C）（c. 1067+ 1G> C）。这导致PTCH的异常剪接。值得注意的是，非典型的隐蔽剪接供体位点被激活，这不符合GT-AG规则。
Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and a predisposition to cancers. Two unrelated patients, 21-and 16-year-old males, with cleft lip and palate and multiple jaw cysts, were diagnosed according to clinical criteria. To confirm a diagnosis of NBCCS, we undertook a molecular genetic analysis of the PTCH gene. Their PTCH genes were analyzed by direct sequencing of the PCR product from their DNA, and previously unreported mutations were identified. A heterozygous duplication at the nucleotide position between 3325 and 3328 of the PTCH gene (c. 3325_3328dupGGCG) was detected in the 21-year-old patient. It caused a frameshift mutation, resulting in a premature termination of the PTCH protein. A point mutation (G to C) in intron 7 of the PTCH gene (c. 1067+ 1G> C) was detected in the 16-year-old patient. This caused an aberrant splicing of PTCH. It is interesting to note that the non-canonical cryptic splice-donor site was activated, which did not conform to the GT–AG rule.