A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine deficiency patients

Abstract

Mutations in the SLC22A5 gene, which encodes for the plasma membrane carnitine transporter OCTN2, cause primary carnitine deficiency (PCD). After our first report of OCTN2 mutations in Chinese, three more Chinese PCD patients were identified. The parents of these families were non-consanguineous and these families were unrelated. Two novel truncating mutations were found: R254X, a single-base mutation at cDNA position 981 (c.981C>T); and Y387X (c.1382T>G). Two probands, one each from Taiwan and Macau, were homozygous for R254X. The other proband from Taiwan carried both R254X and Y387X. Two additional heterozygote carriers of R254X were also identified among 250 control samples, while none was detected for Y387X. The population carrier rate for R254X would be about 1 in 125. Haplotypes of R254X alleles were examined and patients homozygous for R254X were also homozygous for the same haplotype of intragenic and microsatellites markers. Analysis of population frequencies of haplotypes revealed that the chance of 4 chromosomes having arisen as independent events was 0.016. We conclude that R254X is probably a founder mutation in Chinese. Other previously reported mutations found in the Japanese population were also screening in 250 control samples but no carrier was identified, indicating that they were either very rare or not present in Southern Chinese.

Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan

“…Two newborns did not receive the mutation analysis and were lost for follow-up. A prevalent founder mutation, c.981C>T (p.R254X) of the SLC22A5 gene has been identified in Taiwan and in other southern Chinese populations (Tang et al 2002). The estimated incidence of CTD is from 1/62,500 to 1/15,625 (Tang et al 2002;Lee et al 2009), which is higher than the incidence found in our study (1/ 118,543).…”

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…Most of the mothers affected by CUD were asymptomatic . The carrier rate of the more severe CUD mutation in the Southern Chinese population, p.R254X, is approximately 1 in 125 (Tang et al 2002). This mutation represented 50% of all mutations in clinically detected cases of CUD but represented only 30% of all mutations in NBS-detected cases (Lee et al 2010), suggesting a decrease in the severity of the disease in the latter group of patients.…”

Identification of Mutations and Evaluation of Cardiomyopathy in Turkish Patients with Primary Carnitine Deficiency

“…The lack of several transmembrane domains may cause degraded or nonfunctional protein product. R254X, previously described mutation, was reported in Chinese and Saudi Arabians, whereas R282X was a common mutation in Caucasians (Burwinkel et al 1999;Lamhonwah et al 2004;Tang et al 2002;Vaz et al 1999;Wang et al 1999). Other 1-bp deletion c.1009delA (T337Pfs12X) results in a frameshift with Thr337Pro leading to a predicted truncated protein of 347 aa length (Lamhonwah et al 2002).…”