Towards a Better Molecular Diagnosis of FMR1-Related Disorders—A Multiyear Experience from a Reference Lab

Genes

Jolanta Czekajska¹  Daniel Szopa¹  Ewa Obersztyn¹  Sylwia Olimpia Rzońca¹  Danuta Sielska-Rotblum¹  Agnieszka Szpecht-Potocka¹  Jerzy Bal¹  Monika Gos¹  Michał Milewski¹  Anna Abramowicz¹  Aleksandra Landowska¹  Dorota Maciejko¹  Tadeusz Mazurczak¹ 

[1] Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland;

关键词: fragile X syndrome;    FXTAS;    FXPOI;    FMR1;    expansion;    diagnostic;    Southern blot;    pre-screening PCR;    TP-PCR;   

DOI  :  10.3390/genes7090059

来源: DOAJ

【 摘 要 】

The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1) molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5′UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%), 4/43 (9.3%) and 3/11 (27.3%) of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used.

【 授权许可】

Unknown