The utility of multiple genomic technologies for interpretation of modern next generation sequencing: A novel case of three FANCA gene variants resulting in autosomal recessive Fanconi anaemia

IF 2.1 4区 医学 Q3 HEMATOLOGY Blood Cells Molecules and Diseases Pub Date : 2023-09-01 DOI:10.1016/j.bcmd.2023.102762
J. Coleman , A.J. Green , L. Bradley
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Abstract

Fanconi anaemia (FA) is a rare autosomal recessive condition resulting in changes in the FANC gene family. This report describes a case of Fanconi anaemia in a family with complex biallelic variants. The patient is a 32-year-old female diagnosed with FA on cascade testing during childhood with chromosome breakage studies. On examination she had a fixed deformity of the right thumb and the proximal interphalangeal joint was immobile. Her brother shared this radial abnormality and had FA, requiring a bone marrow transplant. She presented in adulthood seeking further BRCA advice and had next generation sequencing that showed three variants in the FANCA gene. One allele a known pathogenic change, the other had two sequence variants in tandem that have been reported as variants of uncertain significance. There is one other unrelated case of these two variants occurring together in cis, resulting in Fanconi anaemia. This case is an interesting example of three variants in the FANCA gene, one allele with a pathogenic deletion and the other with a single complex allele made up of two missense variants of uncertain significance, likely manifesting with FA. It highlights the utility of different genetic technologies in the interpretation of next generation sequencing.

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多种基因组技术在解释现代下一代测序中的应用:三种FANCA基因变异导致常染色体隐性范可尼贫血的新病例
Fanconi贫血症(FA)是一种罕见的常染色体隐性遗传疾病,导致FANC基因家族发生变化。本报告描述了一个具有复杂双等位基因变异的家族中的Fanconi贫血症病例。该患者是一名32岁的女性,在儿童期染色体断裂研究的级联测试中被诊断为FA。经检查,她右手拇指有固定畸形,近端指间关节不动。她的哥哥也有这种放射异常,患有FA,需要进行骨髓移植。她在成年后提出了进一步的BRCA建议,并进行了下一代测序,结果显示FANCA基因有三种变体。一个等位基因是已知的致病性变化,另一个有两个串联的序列变体,这些变体已被报道为具有不确定意义的变体。还有另一种不相关的情况是,这两种变体在顺式中同时发生,导致范科尼贫血。该病例是FANCA基因三种变体的一个有趣例子,一种等位基因具有致病性缺失,另一种具有由两种意义不确定的错义变体组成的单一复杂等位基因,可能表现为FA。它突出了不同遗传技术在下一代测序解释中的实用性。
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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
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