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A dyadic genotype-phenotype approach to diagnostic criteria for Proteus syndrome.
American Journal of Medical Genetics Seminars in Medical Genetics, Part C ( IF 3.1 ) Pub Date : 2019-11-06 , DOI: 10.1002/ajmg.c.31744
Julie C Sapp 1 , Anna Buser 1 , Jasmine Burton-Akright 1 , Kim M Keppler-Noreuil 1, 2 , Leslie G Biesecker 1
Affiliation  

Phenotype-based diagnostic criteria were developed for Proteus syndrome in 1999 and updated in 2006. Subsequently, the causative mosaic gene alteration was discovered, the c.49G>A p.E17K variant in AKT1. As well, a number of overlapping overgrowth disorders attributable to mosaic PIK3CA variants have now been characterized, leading to the designation of PIK3CA-related overgrowth spectrum (PROS). Finally, ongoing work to better characterize Proteus syndrome has led to identification of additional features of that disorder that could be useful in diagnostic criteria. We have taken the opportunity of these discoveries to re-evaluate the Proteus syndrome diagnostic criteria. Here we propose a new set of diagnostic criteria that establishes a weighted, point-based system for the phenotypic attributes and then integrates that with the potential molecular test results to result in one of two designations: AKT1-related Proteus syndrome or AKT1-related overgrowth spectrum. A patient whose only manifestation is an AKT1 c.49G>A-positive tumor would receive neither of these designations. Here we review the rational basis of diagnostic criteria and argue that a unitary diagnostic entity is a distinct gene-phenotype dyad and that this should be the model for all mendelian disorders. The gene-alone or phenotype-alone approach is inadequate to rigorously delineate a unitary diagnostic entity.

中文翻译:

变形杆菌综合征诊断标准的二元基因型-表型方法。

1999 年为变形杆菌综合征制定了基于表型的诊断标准,并于 2006 年更新。随后,发现了致病的镶嵌基因改变,即 AKT1 中的 c.49G>A p.E17K 变体。同样,许多可归因于镶嵌 PIK3CA 变体的重叠过度生长障碍现已被表征,导致指定 PIK3CA 相关过度生长谱 (PROS)。最后,正在进行的更好地表征变形杆菌综合征的工作已经导致识别出该疾病的其他特征,这些特征可能对诊断标准有用。我们利用这些发现的机会重新评估了变形杆菌综合征的诊断标准。在这里,我们提出了一套新的诊断标准,建立了一个加权的,表型属性的基于点的系统,然后将其与潜在的分子测试结果相结合,以产生以下两种名称之一:AKT1 相关变形杆菌综合征或 AKT1 相关过度生长谱。唯一表现是 AKT1 c.49G>A 阳性肿瘤的患者将不会接受这些指定。在这里,我们回顾了诊断标准的合理基础,并认为单一诊断实体是一个独特的基因表型二元组,这应该是所有孟德尔疾病的模型。单独的基因或单独的表型方法不足以严格描述单一的诊断实体。A 阳性肿瘤不会获得这些名称。在这里,我们回顾了诊断标准的合理基础,并认为单一诊断实体是一个独特的基因表型二元组,这应该是所有孟德尔疾病的模型。单独的基因或单独的表型方法不足以严格描述单一的诊断实体。A 阳性肿瘤不会获得这些名称。在这里,我们回顾了诊断标准的合理基础,并认为单一诊断实体是一个独特的基因表型二元组,这应该是所有孟德尔疾病的模型。单独的基因或单独的表型方法不足以严格描述单一的诊断实体。
更新日期:2019-11-01
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