Beware the laboratory report: discrepancy in variant classification on reproductive carrier screening.
Beware the laboratory report: discrepancy in variant classification on reproductive carrier screening.
复制标题
请注意实验室报告：生殖携带者筛查的变异分类存在差异。
DOI：
10.1038/gim.2017.174
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Rose,NancyC
中科院分区：
文献类型：
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作者：
Ramdaney,Aarti;Dunn,DianeM;Weiss,RobertB;Rose,NancyC
To the Editor: Carrier screening in the reproductive setting is designed to screen individuals without a clinical phenotype or family history to provide a risk assessment for genetic disorders. The number of conditions included on current screening panels range from 3 to over 200, with the majority of conditions following autosomal-recessive inheritance. In recent years several X-linked conditions have also been added, such as Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Although carrier screening for DMD and BMD is not specifically recommended by any professional society, including the American College of Medical Genetics and Genomics (ACMG) and the American College for Obstetricians and Gynecologists, it is present on many laboratory panels. We present a prenatal screen in which a laboratory interpretation, had it not undergone further investigation, could have affected clinical outcome. A 32-year-old G2P1001 Caucasian woman at 14 weeks gestation presented for genetic counseling with carrier screening results that reported her to be a carrier for BMD with a likely pathogenic variant. This variant, c. 7850A> G, is also known as NM_004006. 2: c. 8219A> G, p. D2740G in Human Genome Variation Society nomenclature. The laboratory reported that the variant was classified according to ACMG guidelines 1 and had been previously observed in two other individuals with BMD. They reported a 50% risk of having an affected pregnancy, as cell-free DNA screening had predicted a male fetus.However, our own review of this variant showed inconsistencies with its classification. We contacted the original laboratory that first identified the variant and it was clarified that the two individuals reported in the literature were actually the same person: a 31-year-old man with a clinical diagnosis of BMD. Although this supports evidence of pathogenicity, as the patient’s phenotype was highly specific for a disease with a single genetic etiology, functional clinical studies had not been completed. Additional information on this individual’s phenotype was not available and it is presumed that he was lost to follow-up. No other case reports or studies on the variant’s clinical implications could be found in the literature, muscular dystrophy database, or clinical variant databases. Our patient also denied any personal or family history of muscular dystrophy or cardiomyopathy.
