The IVF/PGD Unit, Sheba Medical Center, Tel Hashomer, Israel.
Breast Cancer Unit, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
Breast Cancer Res Treat. 2021 Feb;186(1):259-263. doi: 10.1007/s10549-020-06084-5. Epub 2021 Jan 15.
The co-occurrence or double heterozygosity of pathogenic/likely pathogenic sequence variants (P/LPSVs) in major cancer susceptibility genes has rarely been reported. Such co-occurrence raises the issues of accurate genetic counseling, preferred recommended surveillance scheme, and the use of preimplantation genetic diagnosis (PGD).
A clinical report of an Ashkenazi Jewish (AJ) family with co occurrence of two PSVs in BRCA1 and TP53 and a literature search.
In an AJ family with a substantial history of cancer limited to the maternal side, two siblings co-harbored TP53 (c.733C>A; p.G245S) and the predominant 5266dup BRCA1 mutation, originating from the mother and the father, respectively. PGD is ongoing. Four families were thus far reported as double heterozygotes for both BRCA1/BRCA2 and TP53. Based on the limited available data, it seems that the phenotype in double PSV heterozygotes is not more severe than in single PSV carrier in either gene.
This family highlights the need to genotype both parents, especially in populations with founder mutations, when a BRCA1 mutation is detected in an offspring, regardless of family history. The combination of mutations in these two genes presents a challenge for PGD since both genes are located on chromosome 17.
主要癌症易感性基因中致病性/可能致病性序列变异（P/LPSV）的同时发生或双重杂合性很少有报道。这种同时发生引发了准确遗传咨询、首选推荐监测方案以及使用植入前遗传学诊断（PGD）的问题。
对一个具有 BRCA1 和 TP53 两种 PSV 同时发生的阿什肯纳兹犹太（AJ）家族的临床报告和文献检索。
在一个癌症史仅限于母系的 AJ 家族中，两个兄弟姐妹同时携带 TP53（c.733C>A;p.G245S）和主要的 5266dup BRCA1 突变，分别来自母亲和父亲。PGD 正在进行中。迄今为止，有四个家族被报道为 BRCA1/BRCA2 和 TP53 的双重杂合子。基于有限的可用数据，似乎在这两个基因中，双重 PSV 杂合子的表型并不比单个 PSV 携带者更严重。
这个家族强调了在一个后代中检测到 BRCA1 突变时，即使家族史不明，也需要对父母双方进行基因分型，尤其是在存在创始突变的人群中。这两个基因位于 17 号染色体上，因此这两种基因突变的组合对 PGD 提出了挑战。
