Balmaña Judith, Nomdedéu Josep, Díez Orland, Sabaté Josep Maria, Balil Anna, Pericay Carles, López López Juan José, Brunet Joan, Baiget Montse, Alonso Carmen
Servicio de Oncología Médica, Hospital de la Santa Creu i Sant Pau, Barcelona, España.
Med Clin (Barc). 2002 Oct 19;119(13):497-9. doi: 10.1016/s0025-7753(02)73474-x.
Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, soft-tissue sarcomas and osteosarcomas, acute leukemia, adrenocortical neoplasms and central nervous system tumors. Germline mutations in gene TP53 are identified in a percentage of affected families.
Eight families with aggregation of childhood sarcomas, brain tumors, breast cancers in pre-menopausal women, and renal tumors were screened for TP53 germ-line mutations. SSCP and posterior direct sequencing were performed for genetic analysis. We also report a previously undescribed family with the Li-Fraumeni syndrome carrying a germline mutation.
Seven families fulfilled so-called Li-Fraumeni like criteria and one fulfilled classical criteria. A new germ-line mutation in codon 238 at exon 7 of the gene TP53 was identified in the family fulfilling classical criteria. This mutation has not been previously reported.
The clinical heterogeneity as well as the molecular complexity and consequences of mutation analysis and genetic counseling make it necessary to develop protocols in this area. A multidisciplinary approach is needed; this approach should be coordinated by a Familial Cancer Genetic Counseling Unit.
李-弗劳梅尼综合征是一种常染色体显性遗传病，其特征为早发性乳腺癌、软组织肉瘤和骨肉瘤、急性白血病、肾上腺皮质肿瘤及中枢神经系统肿瘤。部分患病家族中可检测到TP53基因的种系突变。
对8个有儿童肉瘤、脑肿瘤、绝经前女性乳腺癌及肾肿瘤聚集现象的家族进行TP53种系突变筛查。采用单链构象多态性分析（SSCP）及直接测序进行基因分析。我们还报告了一个携带种系突变的、此前未被描述过的李-弗劳梅尼综合征家族。
7个家族符合所谓的类李-弗劳梅尼综合征标准，1个家族符合经典标准。在符合经典标准的家族中，发现了TP53基因第7外显子238密码子处的一个新的种系突变。此前未见该突变的报道。
临床异质性以及突变分析和遗传咨询的分子复杂性与结果，使得有必要在该领域制定相关方案。需要采取多学科方法；该方法应由家族性癌症遗传咨询单位进行协调。
