Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype–phenotype correlation

Yamak, AA; Bitar, Fadi; Karam, Pascale E.; Nemer, Georges

doi:10.1111/j.1399-0004.2007.00814.x

Cited by 23 publications

(20 citation statements)

References 13 publications

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“…This argued for R254X to be a founder mutation in the Lebanese population (2). These eight patients represent the entire population of PCD diagnosed at our hospital.…”

Section: Resultsmentioning

confidence: 92%

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Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

et al. 2013

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Solute carrier family 22 member 5 (SLC22A5) encodes a sodium-dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta-oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature-reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.

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“…This argued for R254X to be a founder mutation in the Lebanese population (2). These eight patients represent the entire population of PCD diagnosed at our hospital.…”

Section: Resultsmentioning

confidence: 92%

“…The human SLC22A5 gene is composed of 10 exons and is located on 5q31 (1,2). The human SLC22A5 gene is composed of 10 exons and is located on 5q31 (1,2).…”

mentioning

confidence: 99%

Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

et al. 2013

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“…Patients with known syndromes (I,e Noonan, DiGeorge, Holt-Oram, Marfan, Alagille, and Char) were excluded from the study. EDTA tubes were used for blood collection and DNA extraction was carried out as previously described [31], [32]. The obtained DNA was quantified at 260 nm and DNA concentration was in the range [400 ng/µl–800 ng/µl].…”

Section: Methodsmentioning

confidence: 99%

Two Heterozygous Mutations in NFATC1 in a Patient with Tricuspid Atresia

et al. 2012

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Tricuspid Atresia (TA) is a rare form of congenital heart disease (CHD) with usually poor prognosis in humans. It presents as a complete absence of the right atrio-ventricular connection secured normally by the tricuspid valve. Defects in the tricuspid valve are so far not associated with any genetic locus, although mutations in numerous genes were linked to multiple forms of congenital heart disease. In the last decade, Knock-out mice have offered models for cardiologists and geneticists to study the causes of congenital disease. One such model was the Nfatc1 −/− mice embryos which die at mid-gestation stage due to a complete absence of the valves. NFATC1 belongs to the Rel family of transcription factors members of which were shown to be implicated in gene activation, cell differentiation, and organogenesis. We have previously shown that a tandem repeat in the intronic region of NFATC1 is associated with ventricular septal defects. In this report, we unravel for the first time a potential link between a mutation in NFATC1 and TA. Two heterozygous missense mutations were found in the NFATC1 gene in one indexed-case out of 19 patients with TA. The two amino-acids changes were not found neither in other patients with CHDs, nor in the control healthy population. Moreover, we showed that these mutations alter dramatically the normal function of the protein at the cellular localization, DNA binding and transcriptional levels suggesting they are disease-causing.

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“…However, cardiomyopathy may develop in isolation or with a milder metabolic presentation during childhood or even older age [4]. Muscle weakness can also be seen.…”

Section: Primary Carnitine Deficiencymentioning

confidence: 98%

Lipid Storage Myopathy

Liang

Nishino

2010

Curr Neurol Neurosci Rep

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Lipid storage myopathy (LSM) is pathologically characterized by prominent lipid accumulation in muscle fibers due to lipid dysmetabolism. Although extensive molecular studies have been performed, there are only four types of genetically diagnosable LSMs: primary carnitine deficiency (PCD), multiple acyl-coenzyme A dehydrogenase deficiency (MADD), neutral lipid storage disease with ichthyosis, and neutral lipid storage disease with myopathy. Making an accurate diagnosis, by specific laboratory tests including genetic analyses, is important for LSM as some of the patients are treatable: individuals with PCD show dramatic improvement with high-dose oral L-carnitine supplementation and increasing evidence indicates that MADD due to ETFDH mutations is riboflavin responsive.

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Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype–phenotype correlation

Cited by 23 publications

References 13 publications

Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

Two Heterozygous Mutations in NFATC1 in a Patient with Tricuspid Atresia

Lipid Storage Myopathy

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