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A novel SLC25A20 splicing mutation in patients of different ethnic origin with neonatally lethal carnitine-acylcarnitine translocase (CACT) deficiency.

Abstract：

:Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder of fatty acid oxidation associated with high mortality. Two female newborns of different ethnic origin (the first Anglo-Celtic and the second Palestinian Arab) both died after sudden collapse on day 2 of life. Both had elevated bloodspot long-chain acylcarnitines consistent with either CACT or carnitine palmitoyltransferase II (CPT2) deficiency; the latter was excluded by demonstrating normal CPT2 activity in fibroblasts. Direct sequencing of all SLC25A20 (CACT) gene exons and exon-intron boundaries revealed that Patient 1 was compound heterozygous for a novel c.609-3c>g (IVS6-3c>g) mutation on the paternal allele and a previously described c.326delG mutation on the maternal allele. Patient 2 was homozygous for the same, novel c.609-3c>g mutation. Previously reported SLC25A20 mutations have been almost exclusively confined to a single family or ethnic group. Analysis of fibroblast cDNA by RT-PCR, agarose gel electrophoresis and sequencing of extracted bands showed that both mutations produce aberrant splicing. c.609-3C>G results in exon 7 skipping leading to a frameshift with premature termination seven amino acids downstream. c.326delG was confirmed to produce skipping of exons 3 or 3 plus 4. CACT activity in both patients' fibroblasts was near-zero. For both families, prenatal diagnosis of an unaffected fetus was performed by mutation analysis on CVS tissue in a subsequent pregnancy. Due to the urgency of prenatal diagnosis in the second family, molecular diagnosis was performed prior to demonstration of CACT enzyme deficiency, illustrating that mutation analysis is a rapid and reliable approach to first-line diagnosis of CACT deficiency.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Korman SH,Pitt JJ,Boneh A,Dweikat I,Zater M,Meiner V,Gutman A,Brivet M

doi

10.1016/j.ymgme.2006.06.009

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

332-8

issue

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(06)00220-4

journal_volume

pub_type

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A novel SLC25A20 splicing mutation in patients of different ethnic origin with neonatally lethal carnitine-acylcarnitine translocase (CACT) deficiency.