Department of Clinical Genetics and Human Genetics, University Medical Centre, Free University of Amsterdam, Amsterdam, The Netherlands.
Fam Cancer. 2012 Dec;11(4):661-5. doi: 10.1007/s10689-012-9553-3.
Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities characterised by cellular cross linker hypersensitivity. FA is caused by mutations in any of so far 15 identified FANC genes, which encode proteins that interact in a common DNA damage response (DDR) pathway. Individuals with FA have a high risk of developing acute myeloid leukaemia (AML) and squamous cell carcinoma. An increased cancer risk has been firmly established for carriers of mutations in FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, RAD51C/FANCO and link the FA pathway to inherited breast and ovarian cancer. We describe a pedigree with FANCD2 mutations c.458T > C (p.Leu153Ser) and c.2715 + 1G > A (p.Glu906LeufsX4) with mild phenotype FA in the index case, T cell ALL in the Leu153Ser heterozygous brother and testicular seminoma in the p.Glu906LeufsX4 heterozygous father. Both FANCD2 alleles were present in the T Cell ALL and the seminoma. This links specific FANCD2 mutations to T cell ALL and seminoma without evidence of allelic loss in the tumour tissue.
范可尼贫血（FA）是一种遗传性疾病，具有先天性和发育性异常特征，表现为细胞交联剂敏感性增加。FA 是由迄今为止鉴定的 15 个 FANC 基因中的任何一个突变引起的，这些基因编码相互作用于共同的 DNA 损伤反应（DDR）途径的蛋白质。FA 患者发生急性髓细胞白血病（AML）和鳞状细胞癌的风险较高。FANCD1/BRCA2、FANCJ/BRIP1、FANCN/PALB2、RAD51C/FANCO 突变携带者的癌症风险增加已得到证实，将 FA 途径与遗传性乳腺癌和卵巢癌联系起来。我们描述了一个家系，该家系中存在 FANCD2 突变 c.458T > C（p.Leu153Ser）和 c.2715 + 1G > A（p.Glu906LeufsX4），先证者表现为轻度 FA 表型，杂合子兄弟患 T 细胞 ALL，杂合子父亲患睾丸精原细胞瘤。在 T 细胞 ALL 和精原细胞瘤中均存在 FANCD2 等位基因。这将特定的 FANCD2 突变与 T 细胞 ALL 和精原细胞瘤联系起来，而肿瘤组织中没有等位基因缺失的证据。
