Neonatal screening of a mutation (R254X) of SLC22A5 (OCTN2) in Primary Carnitine Deficiency
Date Issued
2009
Date
2009
Author(s)
Wu, Chiung-Chuan
Abstract
Mutations in the SLC22A5 gene, which encodes the plasma membrane carnitine transporter OCTN2, cause primary carnitine deficiency (PCD). Currently, PCD is screened in newborns using free carnitine level as a marker. However, owing to the high free carnitine level in the maternal circulation, the affected babies may not have a free carnitine level low enough to be picked up by screening. Previously, the OCTN2 gene c.981 C>T (p.R254X) mutation was found to be common in the Southern Chinese population. Therefore, in this study we want to see if molecular diagnosis could enhance newborn screening of PCD.n this study, we analyzed blood spot DNA OCTN2 gene p.R254X mutation. We first analyzed 348 random anonymous control DNA samples to see the prevance of this mutation in the population. We then analyzed 48 blood spot samples in which free carnitine level was lower than 11µM (the standard cut off for free carnitine was lower than 6.44 μΜ).e found that among the three methods for blood spot DNA extreaction (the methanol method, boiling method, and QIAamp method); the QIAmp method gave the best result. We then found two p.R254X heterozygotes in the 348 control DNA (1in 174); another two p.R254X heterozygotes in the 48 samples with low free carnitine level (1 in 24). In comparison to previous data, newborns with low free carnitine level did have a higher prevalence of OCTN2 gene p.R254X mutation (p=0.01996). Babies who had both low free carnitine and OCTN2 mutation should have a higher chance to be a patient of primary carnitine deficiency, and their disease status should be determined. This method, therefore, increases the sensitivity of detecton of PCD without increase the false positive rate of the screening.
Subjects
Primary carnitine deficiency (PCD)
Dried Blood spot (DBS)
Free carnitine (C0)
OCTN2 Founder hot spot R254X
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