Early onset dystonia (EOD) is associated with a 3bp-(ΔGAG) in-frame deletion in the TOR1A gene, which encodes for torsinA. Carriers of the mutant (ΔGAG) allele can either develop or escape a dystonic phenotype (~30% penetrance). The expression ratio of the two alleles could be important for the manifestation or prevention of the disease since wild-type (WT) torsinA is thought to have protective function. Absence of an antibody discriminating WT from ΔE torsinA has precluded the determination ΔE and WT torsinA levels in manifesting and nonmanifesting carriers. We performed quantitative analysis of TOR1A allele expression in manifesting (MC) and nonmanifesting (NMC) carriers using quantitative allele-specific PCR (qASPCR) to determine the levels of mutant versus WT torsinA mRNA. The technique described showed high degree of specificity in detecting the two alleles. The present study represents the first comprehensive analysis of biallelic expression of the TOR1A gene in lymphoblast and brain samples from patients and NMC relatives. We demonstrate that mRNA is transcribed from both the WT and ΔGAG allele in peripheral and neural tissues with a trend for increased expression of the ΔGAG allele compared to the WT in carriers regardless of their phenotype and thus cannot account for the reduced penetrance. 1. Introduction Most autosomal genes are transcribed from both alleles except those regulated by genomic imprinting [1]. However, nonimprinted autosomal genes can also demonstrate unequal expression of their two alleles due to cis acting polymorphisms in their promoter, enhancer, or other regulatory regions linked to one of the two alleles, selectively affecting its transcription and/or mRNA stability/processing, including splicing and turnover [2, 3]. In fact, it has been estimated that among human brain expressed genes, approximately 20% exhibit unequal expression of the two alleles [2–4]. This phenomenon is termed “allelic imbalance,” and examples of genes showing allelic imbalance include the serotonin transporter (SLC6A4) [5], the mu opioid receptor (OPRM1) [6], and the multidrug resistance polypeptide 1 (MDR1, ABCB1) [7]. Allelic imbalance in gene expression is of particular importance in carriers of a mutant allele associated with a genetic disease. Early onset dystonia (EOD) is associated with a 3？bp-(ΔGAG) in-frame deletion in the TOR1A gene [8], which encodes for torsinA [9]. Individuals heterozygous for the mutant (ΔGAG) allele can either develop or escape a dystonic phenotype (~30% penetrance) [10]. The expression ratio of the two alleles could
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