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Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings
Author(s) -
Yener İnci Hande,
Topaloglu Haluk,
ErdemÖzdamar Sevim,
DayangacErden Didem
Publication year - 2017
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.13052
Subject(s) - sma* , spinal muscular atrophy , phenotype , gene , medicine , gene expression , transcriptome , genetics , biology , mathematics , combinatorics
Background In single gene disorders, patients with the same genotype may have variations in severity. One of the main factors affecting disease severity is modifier genes. Spinal muscular atrophy ( SMA ) is an autosomal recessive neuromuscular disorder caused by degeneration of alpha motor neurons. Plastin 3 ( PLS 3 ) is a phenotypic modifier of SMA , and neuritin 1 ( NRN 1 ) has also been suggested as a possible modifier gene. The aim of the present study was therefore to analyze PLS 3 and NRN 1 expression in SMA siblings in four families. Methods The study group consisted of four SMA families with seven with discordant phenotype and two affected siblings. Total RNA was isolated from whole blood. PLS 3 and NRN 1 expression was analyzed on quantitative real‐time polymerase chain reaction. Results In family 1 only NRN 1 expression was increased in the mildly affected sister. In family 2 only PLS 3 had a modifier effect. Family 3, which had type III siblings with identical clinical phenotypes, had similar PLS 3 expression between the siblings but no NRN 1 expression. In family 4, neither PLS 3 nor NRN 1 had any correlation with severity. Conclusion On analysis of the expression of NRN 1 in SMA patients for the first time, NRN 1 could be a potential modifier gene. PLS 3 expression does not always modify SMA phenotype. In patients with no modifier effect of known genes, genome sequencing and transcriptome analysis are promising for the identification of novel modifiers and understanding of SMA pathophysiology.