背景:宪法性错配修复缺陷(CMMRD)是由错配修复基因之一的双等位基因致病变体引起的,并导致早发性结肠直肠癌,白血病,脑肿瘤和其他儿童恶性肿瘤。在这里,我们报告了一个在MSH6基因中具有复合杂合变体的CMMRD病例,包括多种结直肠癌的从头变异。
方法:一个11岁的女孩,从出生起就出现了多个类似于咖啡馆的斑点,出现腹痛,两个月以上的腹泻和血便。结肠镜检查显示多发结肠息肉,包括一个大的上皮肿瘤,病理检查提示为管状腺癌。脑磁共振成像(MRI)显示一个不明的明亮物体(UBO),常见于1型神经纤维瘤病(NF1)。基因检测显示复合杂合变异,c.[2969T>A(第Leu990*)]和[3064G>T(p.MSH6基因中的Glu1022*)];c.2969T>A(p。Leu990*)被鉴定为从头变体。
结论:我们首次报道一例CMMRD患者在MSH6中出现从头变异,在儿童时期发展为结直肠癌。CMMRD症状通常类似于NF1,如这里所观察到的。医师应熟悉CMMRD临床表型,以筛查和早期发现癌症。
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is caused by biallelic pathogenic variants in one of the mismatch repair genes, and results in early onset colorectal cancer, leukemia, brain tumors and other childhood malignancies. Here we report a
case of CMMRD with compound heterozygous variants in the MSH6 gene, including a de novo variant in multiple colorectal cancers.
METHODS: An 11-year-old girl, who presented with multiple spots resembling café-au-lait macules since birth, developed abdominal pain, diarrhea and bloody stool over two months. Colonoscopy revealed multiple colonic polyps, including a large epithelial tumor, and pathological examination revealed tubular adenocarcinoma. Brain magnetic resonance imaging (MRI) showed an unidentified bright object (UBO), commonly seen in neurofibromatosis type 1 (NF1). Genetic testing revealed compound heterozygous variants, c. [2969T > A (p.Leu990*)] and [3064G > T (p.Glu1022*)] in the MSH6 gene; c.2969T > A (p.Leu990*) was identified as a de novo variant.
CONCLUSIONS: We present the first report of a CMMRD patient with a de novo variant in MSH6, who developed colorectal cancer in childhood. CMMRD symptoms often resemble NF1, as observed here. Physicians should become familiar with CMMRD clinical phenotypes for the screening and early detection of cancer.