Towards a Better Molecular Diagnosis of FMR1-Related Disorders-A Multiyear Experience from a Reference Lab.
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.
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. sylwia.rzonca@imid.med.pl.
Sylwia Olimpia
SO
Rzońca
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. monika.gos@imid.med.pl.
Monika
M
Gos
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. daniel26a@wp.pl.
Daniel
D
Szopa
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. d.sielska-rotblum@czd.pl.|Department of Medical Genetics, Children's Memorial Health Institute, 20 Al. Dzieci Polskich Street, 04-730 Warsaw, Poland. d.sielska-rotblum@czd.pl.
Danuta
D
Sielska-Rotblum
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. aleksandra.landowska@imid.med.pl.
Aleksandra
A
Landowska
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. aspotocka@o2.pl.|Medgen, 27 Orzycka Street, 02-659 Warsaw, Poland. aspotocka@o2.pl.
Agnieszka
A
Szpecht-Potocka
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. michal.milewski@imid.med.pl.
Michał
M
Milewski
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. jolanta.czekajska@imid.med.pl.
Jolanta
J
Czekajska
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. anna.abramowicz@imid.med.pl.
Anna
A
Abramowicz
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. ewa.obersztyn@imid.med.pl.
Ewa
E
Obersztyn
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. dorota.maciejko@wum.edu.pl.|Department of Immunology, Biochemistry and Nutrition, Medical University of Warsaw, 61 Żwirki Wigury Street, 02-091 Warsaw, Poland. dorota.maciejko@wum.edu.pl.
Dorota
D
Maciejko
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. t.mazurczak@wp.pl.|The Maria Grzegorzewska Academy of Special Education, 40 Szczęśliwicka Street, 02-353 Warsaw, Poland. t.mazurczak@wp.pl.
Tadeusz
T
Mazurczak
Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland. jerzy.bal@imid.med.pl.
Jerzy
J
Bal
FMR1; FXPOI; FXTAS; Southern blot; TP-PCR; diagnostic; expansion; fragile X syndrome; pre-screening PCR