A clinical case of multilocus imprinting disturbances: the first description in the Russian Federation

Abstract

Multilocus imprinting disturbances (MLID) is a molecular subtype of imprinting disorders (IDs), in which multiple methylation abnormalities of imprinted regions and genes are observed in combination with polymorphic clinical manifestations, including overlapping phenotypic features of individual imprinting disorders. The causes of MLID are mutations in genes encoding oocyte and zygotic factors of embryo development, which increases the risk of recurrent birth of children with imprinting disorders in mothers carrying such mutations. Due to the need to understand the exact risk for repeated childbirth, it is advisable to diagnose MLID in patients with an ambiguous phenotype and a negative result of studies on individual imprinting disorders, followed by a search for mutations in MLID-associated genes. The purpose of the work is to describe the clinical and epigenetic characteristics of a patient with MLID. A clinical case of a comorbid patient aged 12 years with an established molecular genetic diagnosis of MLID by the method of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is presented. The features of the patient’s phenotype allow us to demonstrate the effect of hypomethylation of several differentially methylated regions of imprinted genes on the formation of a polymorphic phenotype, including overlapping signs of individual imprinting disorders, and to assess the difficulty of making an unambiguous clinical diagnosis for this patient. Pronounced clinical polymorphism, negative results of previously conducted molecular genetic studies on certain forms of imprinting disorders allow us to consider the MLID study as a first-line test for the diagnosis of methylation abnormalities in MLID and imprinting disorders.