Dataset Information

A novel homozygous missense SLC25A20 mutation in three CACT-deficient patients: clinical and autopsy data.

ABSTRACT: Carnitine-acylcarnitine translocase (CACT) deficiency is a fatty acid ß-oxidation disorder of the carnitine shuttle in mitochondria, with a high mortality rate in childhood. We evaluated three patients, including two siblings, with neonatal-onset CACT deficiency and revealed identical homozygous missense mutations of p.Arg275Gln within the SLC25A20 gene. One patient died from hypoglycemia and arrhythmia at 26 months; his pathological autopsy revealed increased and enlarged mitochondria in the heart but not in the liver.

SUBMITTER: Chinen Y

PROVIDER: S-EPMC7162975 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A novel homozygous missense <i>SLC25A20</i> mutation in three CACT-deficient patients: clinical and autopsy data.

Chinen Yasutsugu Y Yanagi Kumiko K Nakamura Sadao S Nakayama Noriko N Kamiya Motoko M Nakayashiro Mami M Kaname Tadashi T Naritomi Kenji K Nakanishi Koichi K

Human genome variation 20200416

Carnitine-acylcarnitine translocase (CACT) deficiency is a fatty acid ß-oxidation disorder of the carnitine shuttle in mitochondria, with a high mortality rate in childhood. We evaluated three patients, including two siblings, with neonatal-onset CACT deficiency and revealed identical homozygous missense mutations of p.Arg275Gln within the <i>SLC25A20</i> gene. One patient died from hypoglycemia and arrhythmia at 26 months; his pathological autopsy revealed increased and enlarged mitochondria in ...[more]

PMID: 32337051

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Project description:PurposeRetinitis pigmentosa (RP) is an inherited retinal disorder that results in the degeneration of photoreceptor cells, ultimately leading to severe visual impairment. We characterized a consanguineous family from Southern India wherein a 25 year old individual presented with night blindness since childhood. The purpose of this study was to identify the causative mutation for RP in this individual as well as characterize how the mutation may ultimately affect protein function.MethodsWe performed a complete ophthalmologic examination of the proband followed by exome sequencing. The likely causative mutation was identified and modeled in cultured cells, evaluating its expression, solubility (both with western blotting), subcellular distribution, (confocal microscopy), and testing whether this variant induced endoplasmic reticulum (ER) stress (quantitative PCR [qPCR] and western blotting).ResultsThe proband presented with generalized and parafoveal retinal pigmented epithelium (RPE) atrophy with bone spicule-like pigmentation in the midperiphery and arteriolar attenuation. Optical coherence tomography scans through the macula of both eyes showed atrophy of the outer retinal layers with loss of the ellipsoid zone, whereas the systemic examination of this individual was normal. The proband's parents and sibling were asymptomatic and had normal funduscopic examinations. We discovered a novel homozygous p.Pro388Ser mutation in the tubby-like protein 1 (TULP1) gene in the individual with RP. In cultured cells, the P388S mutation does not alter the subcellular distribution of TULP1 or induce ER stress when compared to wild-type TULP1, but instead significantly lowers protein stability as indicated with steady-state and cycloheximide-chase experiments.ConclusionsThese results add to the list of known mutations in TULP1 identified in individuals with RP and suggest a possible unique pathogenic mechanism in TULP1-induced RP, which may be shared among select mutations in TULP1.

Dataset Information

A novel homozygous missense SLC25A20 mutation in three CACT-deficient patients: clinical and autopsy data.

Publications

A novel homozygous missense <i>SLC25A20</i> mutation in three CACT-deficient patients: clinical and autopsy data.

Similar Datasets

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