Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Randwick, NSW, Australia.
School of Women's and Children's Health, University of New South Wales, Randwick, NSW, Australia.
Eur J Hum Genet. 2021 Jan;29(1):79-87. doi: 10.1038/s41431-020-0685-x. Epub 2020 Jul 16.
Reproductive genetic carrier screening aims to offer couples information about their chance of having children with certain autosomal recessive and X-linked genetic conditions. We developed a gene list for use in "Mackenzie's Mission", a research project in which 10,000 couples will undergo screening. Criteria for selecting genes were: the condition should be life-limiting or disabling, with childhood onset, such that couples would be likely to take steps to avoid having an affected child; and/or be one for which early diagnosis and intervention would substantially change outcome. Strong evidence for gene-phenotype relationship was required. Candidate genes were identified from OMIM and via review of 23 commercial and published gene lists. Genes were reviewed by 16 clinical geneticists using a standard operating procedure, in a process overseen by a multidisciplinary committee which included clinical geneticists, genetic counselors, an ethicist, a parent of a child with a genetic condition and scientists from diagnostic and research backgrounds. 1300 genes met criteria. Genes associated with non-syndromic deafness and non-syndromic differences of sex development were not included. Our experience has highlighted that gene selection for a carrier screening panel needs to be a dynamic process with ongoing review and refinement.
生殖遗传携带者筛查旨在为夫妇提供有关生育某些常染色体隐性和 X 连锁遗传疾病患儿的机会的信息。我们开发了一个基因列表，用于“Mackenzie's Mission”研究项目，该项目将对 10000 对夫妇进行筛查。选择基因的标准是：疾病应具有生命限制或致残性，且发病于儿童期，以便夫妇可能会采取措施避免生育受影响的孩子；和/或对于这种疾病，早期诊断和干预会显著改变结果。需要有强有力的基因表型关系证据。候选基因是从 OMIM 中确定的，并且通过对 23 个商业和已发表的基因列表进行了审查。临床遗传学家使用标准操作程序对基因进行了审查，由包括临床遗传学家、遗传咨询师、伦理学家、患有遗传疾病的儿童的父母和来自诊断和研究背景的科学家在内的多学科委员会监督了这一过程。有 1300 个基因符合标准。未包括与非综合征性耳聋和非综合征性性别发育差异相关的基因。我们的经验表明，用于携带者筛查面板的基因选择需要是一个具有持续审查和完善的动态过程。
