Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: A novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality

Burwinkel, B Kreuder, J Schweitzer, S Vorgerd, M Gempel, K Gerbitz, KD Kilimann, MW

B. Burwinkel et al., Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: A novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality, BIOC BIOP R, 261(2), 1999, pp. 484-487

19

INGLESE

Article

Biochemistry & Biophysics

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

0006-291X → ACNP

261

2

1999

484 - 487

ISI

0006-291X(19990802)261:2<484:CTOMIS>2.0.ZU;2-9

Systemic primary carnitine deficiency (CDSP, MIM 212140) is a disorder of f atty acid oxidation manifesting in acute metabolic decompensation or in pro gressive cardiomyopathy and muscle weakness. Mutations in the plasmalemmal organic cation/carnitine transporter OCTN2 were recently identified in CDSP patients of diverse ethnic backgrounds. We have performed OCTN2 mutation a nalysis in two unrelated German patients with primary carnitine deficiency and identified three molecular abnormalities. On one of the four chromosome s analyzed, we detected an Arg169Gln missense mutation that affects an argi nine residue absolutely conserved in the entire transporter superfamily to which OCTN2 belongs. On the three other chromosomes, we found an Arg282ter nonsense mutation in exon 5. This mutation is embedded into different haplo types of closely spaced intragenic dimorphisms in our two patients and was recently described in a patient of Asiatic Indian background, so it appears to be a recurrent or ancient founder mutation that may account for more CD SP cases. Finally, we found that the Arg282ter nonsense mutation is associa ted with a splicing abnormality at the intron 6/exon 7 junction. However, n o mutations are present in exon 6, intron 6, or exon 7, suggesting that def ective splicing of exon 7 on the Arg282ter allele is due to an unconvention al, long-distance mechanism. (C) 1999 Academic Press.