Dataset Information

Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5 Caused by the Founder Variant p.(Glu87Lys) in ISCA1.

ABSTRACT: Iron-sulfur cluster assembly 1 (ISCA1) is one of the essential proteins operating in the mitochondrial iron-sulfur (Fe-S) cluster biogenesis pathway. We reported the variant c.259G?>?A [p.(Glu87Lys)] in homozygous state in exon 4 of the ISCA1 gene as the likely cause of multiple mitochondrial dysfunction syndrome 5 in a previous publication. We now report the third patient with the same phenotype and variant, further supporting the possibility of a founder event. Our observation confirms the clinical presentation associated with a probable founder variant in this condition.

SUBMITTER: Shukla A

PROVIDER: S-EPMC6087475 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5 Caused by the Founder Variant p.(Glu87Lys) in <i>ISCA1</i>.

Shukla Anju A Kaur Parneet P Girisha Katta M KM

Journal of pediatric genetics 20180405 3

Iron-sulfur cluster assembly 1 (ISCA1) is one of the essential proteins operating in the mitochondrial iron-sulfur (Fe-S) cluster biogenesis pathway. We reported the variant c.259G > A [p.(Glu87Lys)] in homozygous state in exon 4 of the <i>ISCA1</i> gene as the likely cause of multiple mitochondrial dysfunction syndrome 5 in a previous publication. We now report the third patient with the same phenotype and variant, further supporting the possibility of a founder event. Our observation confirms ...[more]

PMID: 30105122

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Project description:BackgroundMarfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1-0.2‰. The causative variant of FNB1 gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis.Case presentationThe patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient.ConclusionsIn this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.

Dataset Information

Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5 Caused by the Founder Variant p.(Glu87Lys) in ISCA1.

Publications

Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5 Caused by the Founder Variant p.(Glu87Lys) in <i>ISCA1</i>.

Similar Datasets

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