Genetic Modifiers of Non-Penetrance and RNA Expression Levels in PRPF31-Associated Retinitis Pigmentosa in a Danish Cohort
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Genetic Modifiers of Non-Penetrance and RNA Expression Levels in PRPF31-Associated Retinitis Pigmentosa in a Danish Cohort. / Lisbjerg, Kristian; Grønskov, Karen; Bertelsen, Mette; Møller, Lisbeth Birk; Kessel, Line.
In: Genes, Vol. 14, No. 2, 435, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic Modifiers of Non-Penetrance and RNA Expression Levels in PRPF31-Associated Retinitis Pigmentosa in a Danish Cohort
AU - Lisbjerg, Kristian
AU - Grønskov, Karen
AU - Bertelsen, Mette
AU - Møller, Lisbeth Birk
AU - Kessel, Line
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - (1) Background/aims: To examine potential genetic modifiers of disease penetrance in PRPF31-associated retinitis pigmentosa 11 (RP11). (2) Methods: Blood samples from individuals (n = 37) with PRPF31 variants believed to be disease-causing were used for molecular genetic testing and, in some cases (n = 23), also for mRNA expression analyses. Medical charts were used to establish if individuals were symptomatic (RP) or asymptomatic non-penetrant carriers (NPC). RNA expression levels of PRPF31 and CNOT3 were measured on peripheral whole blood using quantitative real-time PCR normalized to GAPDH. Copy number variation of minisatellite repeat element 1 (MSR1) was performed with DNA fragment analysis. (3) Results: mRNA expression analyses on 22 individuals (17 with RP and 5 non-penetrant carriers) revealed no statistically significant differences in PRPF31 or CNOT3 mRNA expression levels between individuals with RP and non-penetrant carriers. Among 37 individuals, we found that all three carriers of a 4-copy MSR1 sequence on their wild-type (WT) allele were non-penetrant carriers. However, copy number variation of MSR1 is not the sole determinant factor of non-penetrance, as not all non-penetrant carriers carried a 4-copy WT allele. A 4-copy MSR1 mutant allele was not associated with non-penetrance. (4) Conclusions: In this Danish cohort, a 4-copy MSR1 WT allele was associated with non-penetrance of retinitis pigmentosa caused by PRPF31 variants. The level of PRPF31 mRNA expression in peripheral whole blood was not a useful indicator of disease status.
AB - (1) Background/aims: To examine potential genetic modifiers of disease penetrance in PRPF31-associated retinitis pigmentosa 11 (RP11). (2) Methods: Blood samples from individuals (n = 37) with PRPF31 variants believed to be disease-causing were used for molecular genetic testing and, in some cases (n = 23), also for mRNA expression analyses. Medical charts were used to establish if individuals were symptomatic (RP) or asymptomatic non-penetrant carriers (NPC). RNA expression levels of PRPF31 and CNOT3 were measured on peripheral whole blood using quantitative real-time PCR normalized to GAPDH. Copy number variation of minisatellite repeat element 1 (MSR1) was performed with DNA fragment analysis. (3) Results: mRNA expression analyses on 22 individuals (17 with RP and 5 non-penetrant carriers) revealed no statistically significant differences in PRPF31 or CNOT3 mRNA expression levels between individuals with RP and non-penetrant carriers. Among 37 individuals, we found that all three carriers of a 4-copy MSR1 sequence on their wild-type (WT) allele were non-penetrant carriers. However, copy number variation of MSR1 is not the sole determinant factor of non-penetrance, as not all non-penetrant carriers carried a 4-copy WT allele. A 4-copy MSR1 mutant allele was not associated with non-penetrance. (4) Conclusions: In this Danish cohort, a 4-copy MSR1 WT allele was associated with non-penetrance of retinitis pigmentosa caused by PRPF31 variants. The level of PRPF31 mRNA expression in peripheral whole blood was not a useful indicator of disease status.
KW - CNOT3
KW - gene expression
KW - MSR1
KW - non-penetrance
KW - PRPF31
KW - retinitis pigmentosa
KW - RP11
UR - http://www.scopus.com/inward/record.url?scp=85148895739&partnerID=8YFLogxK
U2 - 10.3390/genes14020435
DO - 10.3390/genes14020435
M3 - Journal article
C2 - 36833363
AN - SCOPUS:85148895739
VL - 14
JO - Genes
JF - Genes
SN - 2073-4425
IS - 2
M1 - 435
ER -
ID: 366047534