Allelic heterogeneity of Proteus syndrome

被引：7

作者：

Buser, Anna ^{[1
]}

Lindhurst, Marjorie J. ^{[1
]}

Kondolf, Hannah C. ^{[1
,2
]}

Yourick, Miranda R. ^{[1
,3
]}

Keppler-Noreuil, Kim M. ^{[1
,4
]}

Sapp, Julie C. ^{[1
]}

Biesecker, Leslie G. ^{[1
]}

机构：

[1] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA

[2] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA

[3] Univ Maryland, Dept Biol, College Pk, MD 20742 USA

[4] Childrens Natl Med Ctr, Washington, DC 20010 USA

来源：

COLD SPRING HARBOR MOLECULAR CASE STUDIES | 2020年 / 6卷 / 03期

关键词：

HEMIHYPERTROPHY; OVERGROWTH; MUTATION; GENOMICS; AKT1; NEVI;

D O I：

10.1101/mcs.a005181

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Proteus syndrome is a mosaic disorder that can cause progressive postnatal over-growth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively associated with the mosaic c.49G > A p.(Glu17Lys) pathogenic variant in AKT1, a variant that is also present in many cancers. Here we describe an individual with severe Proteus syndrome who died at 7.5 yr of age from combined parenchymal and restrictive pulmonary disease. Remarkably, this individual was found to harbor a mosaic c.49_50delinsAG p.(Glu17Arg)variant in AKT1 at a variant allele fraction that ranged from <0.01 to 0.46 in fibroblasts established from an overgrown digit. This variant was demonstrated to be constitutively activating by phosphorylation of AKT(S473). These data document allelic heterogeneity for Proteus syndrome. We recommend that individuals with a potential clinical diagnosis of Proteus syndrome who are negative for the p.(Glu17Lys) variant be tested for other variants in AKT1.

引用

页数：10

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