Menko Fred H, Kaspers Gertjan L, Meijer Gerrit A, Claes Kathleen, van Hagen Johanna M, Gille Johan J P
Department of Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Fam Cancer. 2004;3(2):123-7. doi: 10.1023/B:FAME.0000039893.19289.18.
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition due to heterozygous germline mutations in DNA mismatch repair genes, in particular MLH1, MSH2 and MSH6. Recently, a syndrome was recognized in which children develop haematological malignancies, solid tumours and signs of neurofibromatosis type 1 due to bi-allelic MMR gene mutations in MLH1, MSH2 and PMS2. Here we describe the child of healthy consanguineous parents who had café-au-lait spots, oligodendroglioma, and rectal cancer. The patient was homozygous for the MSH6 mutation c.3386_3388delGTG in exon 5 which has a predicted pathogenic effect. Germline NF1 gene mutation testing was negative. The rectal tumour showed microsatellite instability and absence of MSH6 staining, whereas the brain tumour was MSI stable and showed normal immunohistochemical expression of MSH6. Apparently, not only MLH1, MSH2 and PMS2, but also MSH6 is involved in the syndrome of childhood cancer and signs of neurofibromatosis type 1.
遗传性非息肉病性结直肠癌（HNPCC）是一种常染色体显性遗传病，由DNA错配修复基因中的杂合子种系突变引起，特别是MLH1、MSH2和MSH6。最近，一种综合征被识别出来，在这种综合征中，由于MLH1、MSH2和PMS2中的双等位基因MMR基因突变，儿童会发生血液系统恶性肿瘤、实体瘤和1型神经纤维瘤病的体征。在此，我们描述了一对健康近亲父母的孩子，该孩子有咖啡牛奶斑、少突胶质细胞瘤和直肠癌。患者外显子5中MSH6突变c.3386_3388delGTG为纯合子，该突变具有预测的致病作用。种系NF1基因突变检测为阴性。直肠肿瘤显示微卫星不稳定且无MSH6染色，而脑肿瘤微卫星稳定且显示MSH6正常免疫组化表达。显然，不仅MLH1、MSH2和PMS2，而且MSH6也与儿童癌症综合征和1型神经纤维瘤病体征有关。
