Abstract
BackgroundPremature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called trinucleotide expansion diseases. Our aim was to analyse the relationship between the paternally inherited premutation (PIP) and the maternally inherited premutation (MIP) by the examination of the family members of women with POF, carrying the premutation allele confirmed by molecular genetic testing.MethodsMolecular genetic testing was performed in the patients of the 1st Department of Obstetrics and Gynecology with suspected premature ovarian failure. First we performed the southern blot analyses and for the certified premutation cases we used the Repeat Primed PCR.ResultsDue to POF/POI, a total of 125 patients underwent genetic testing. The FMR1 gene trinucleotide repeat number was examined in the DNA samples of the patients, and in 15 cases (12%) deviations (CGG repeat number corresponding to premutation or gray zone) were detected. In 6 cases out of the 15 cases the CGG repeat number fell within the range of the so-called gray zone (41–54 CGG repeat) (4.8%, 6/125), and the FMR1 premutation (55–200 CGG repeat) ratio was 7.2% (9/125). In 4 out of the 15 cases we found differences in both alleles, one was a premutation allele, and the other allele showed a repeat number belonging to the gray zone. Out of 15 cases, only maternal inheritance (MIP) was detected in 2 cases, in one case the premutation allele (91 CGG repeat number), while in the other case an allele belonging to the gray zone (41 CGG repeat number) were inherited from their mothers. In 10 out of 15 cases, the patient inherited the premutation allele only from the father (PIP). In 5 out of the 10 cases (50%) the premutation allele was inherited from the father, and the repeat number ranged from 55 to 133. Out of 125 cases, 9 patients had detectable cytogenetic abnormalities (7.2%).ConclusionsThe RP-PCR method can be used to define the smaller premutations and the exact CGG number. Due to the quantitative nature of the RP-PCR, it is possible to detect the mosaicism as well.
Highlights
Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called trinucleotide expansion diseases
The FMR1 gene mutation is an associated disease, belonging to the so-called trinucleotid expansion diseases group. These diseases, Fragile X Syndrome (FRAXA) (Fragile X syndrome), premature ovarian failure (POF)/POI and Fraxa X Associated Tremor/Ataxia Syndrome (FXTAS) are associated with a CGG repeats expansion, which is located at the FMR1 gene promoter region
We examined the FMR1 gene trinucleotide repeat number in DNA samples of the patients, and in 15 cases (12%) we detected deviations (CGG repeat number corresponding to premutation or gray zone)
Summary
Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called trinucleotide expansion diseases. The FMR1 gene mutation is an associated disease, belonging to the so-called trinucleotid expansion diseases group. These diseases, FRAXA (Fragile X syndrome), POF/POI (premature ovarian failure) and FXTAS (tremor/ataxia syndrome) are associated with a CGG repeats expansion, which is located at the FMR1 gene promoter region. The FMR1 gene encodes the protein FMRP, which is an RNA binding protein and plays a significant role in the transport processes of RNA, stabilization of RNA molecules, and mRNA translation. Studies proved in fruit flies and mice, that due to the lack of the FMRP protein some translational disturbances occur, which affect the early neuronal development, neurotransmission processes and synaptic connections
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