Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway

The Journal of Molecular Diagnostics : JMD
Gozde AkgumusMarilyn M Li

Abstract

Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, and megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes are caused by somatic variants in the genes associated with the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, resulting in a spectrum of overgrowth syndromes with overlapping features that could be difficult to distinguish based on phenotypic presentations alone. In addition, Sanger sequencing is ineffective for the detection of a causal variant because of the mosaic nature of these variants, whereas targeted next-generation sequencing technology offers a deeper sequencing coverage and allows the detection of low-level mosaicism. Recent studies have shown that the causal variants are only present i...Continue Reading

Citations

Feb 15, 2019·Molecular Genetics & Genomic Medicine·Emilie LalondeArupa Ganguly
Jun 28, 2019·Current Opinion in Pediatrics·Miguel Zúñiga-CastilloJoyce M C Teng
Jul 11, 2018·Clinical Case Reports·Virginia ValentiniLaura Ottini
Sep 22, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Peter Rotwein
Dec 16, 2020·Development·Mark PerfettoShuo Wei
May 19, 2021·Calcified Tissue International·Ali Al KaissiRudolf Ganger

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