Genetic variants in cardiac calcification in Northern Sweden

Hellman, Urban; Mörner, Stellan; Henein, Michael Y.

doi:10.1097/md.0000000000015065

Cited by 3 publications

(3 citation statements)

References 26 publications

(27 reference statements)

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“…The WGS demonstrated that this patient is heterozygous in the ABCC6 gene for a maternally-inherited sequence variant. This variant has been reported in the heterozygous state in a patient with calcific coronary artery disease and hypertonia; however, further evidence of pathogenicity was not provided [5]. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.…”

Section: Discussionmentioning

confidence: 94%

Mild Ocular Findings and Skeletal Anomalies Producing a Marfanoid Appearance, Along with Autoimmune/Inflammatory Findings Due to SNV of Unknown Significance in Genes ABCC6 and OPA1 Inherited from the Mother

Lacassie

2022

WJOVR

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When faced with patients presenting with dolichostenomelia, ocular features, and Marfanoid appearance, most physicians often suspect the possibility of Marfan syndrome or one of its differential diagnoses. We report a 14-year-old Hispanic female with nanophthalmos with high hyperopia, dolichostenomelic appearance, mild musculoskeletal findings, xerosis, and positivity for some inflammatory/autoimmune markers. Although a detailed evaluation at age eight showed a Marfan systemic score of 0 and growth only between the 10 th and 25 th centile, the diagnosis of Marfan syndrome has been frequently raised until now. Without a specific diagnosis that could explain her syndromic findings, whole genome sequencing (WGS) was requested. This study did not detect a known reported variant but rather heterozygote single nucleotide variants in genes ABCC6 and OPA1 were found. These variants were inherited from her mother who also presents with some medical issues and positive antinuclear antibodies. Although these variants might explain these clinical findings, further confirmation will be necessary. We hope this report may encourage subsequent publications.

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Section: Discussionmentioning

confidence: 94%

Mild Ocular Findings and Skeletal Anomalies Producing a Marfanoid Appearance, Along with Autoimmune/Inflammatory Findings Due to SNV of Unknown Significance in Genes ABCC6 and OPA1 Inherited from the Mother

Lacassie

2022

WJOVR

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“…The pumping of ATP from intracellular to extracellular are mediated primarily by ABCC6 of hepatocytes ( 7 ). Variants or other types of defects in ABCC6 lead to ectopic calcification ( 10 – 12 ). In addition, variants in ABCC6 may affect its membrane localization, leading to functional impairment ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel Idiopathic Atrial Calcification: Pathologic Manifestations and Potential Mechanism

Liu

Chen

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCardiac calcification is a type of ectopic pathologic calcification of unknown etiology and mechanisms. Once diagnosed, the location, extent and morphology of the calcified lesions, as well as their functional significance in the heart, are usually the focus of case reports. Calcification is mostly distributed in myocardium, but rarely reported in atrium. In addition, because of limited sampling and complex pathological mechanisms, the etiology underlying the formation of these calcified lesions also remains unclear.MethodsTwo cardiac calcifications were found in a patient, died of trauma-induced subarachnoid hemorrhage after slightly drinking, during a standard autopsy. The location and morphological characteristics of the calcified lesions were determined by computed tomography (CT) and CT-based 3D reconstruction. The specific histopathological characteristics of the lesions were determined by multi-staining. The concentration of free calcium and inorganic pyrophosphate (PPi) in plasma reflected the change of calcium metabolism. The expression and membranal localization of the ATP Binding Cassette Subfamily C Member 6 (ABCC6) in hepatocytes were detected by immunofluorescence. The variants of the ABCC6 were detected by Sanger sequencing and potential pathogenic variants were further identified by in silico analysis.ResultsThe present study describes a patient with idiopathic calcification with two pear-shaped and irregularly hollow lesions symmetrically distributed in the patient's atrium. Massive accumulation of calcium salts was identified by multi-staining. For this patient, the plasma concentration of free calcium was higher than the control, indicating that calcium metabolism was disturbed. Furthermore, the plasma PPi of the patient was lower than the normal. By using immunofluorescence, the expression and membranal localization of ABCC6 was decreased and impaired in hepatocytes, respectively. Combined with Sanger sequencing and in silico analysis, 7 variants were identified.ConclusionsThis study described a novel patient with symmetrically distributed idiopathic atrial calcifications. Furthermore, all the results indicated that these pathologic calcifications may be secondary to reduced plasma PPi content due to ABCC6 dysfunction in hepatocytes. Moreover, these findings provided novel clues to the pathogenesis, clinical diagnosis and treatment of idiopathic atrial calcification in future.

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“…In a pilot study, we attempted to identify the key genetic variants in candidate genes which may predispose to coronary arterial stiffness, mostly caused by calcification pathology and whether there is any impact of gender on this potential relationship [9]. We investigated three candidate genes, ENPP1, ABCC6 and NT5E involved in pyrophosphate (PPi) and inorganic phosphate…”

Section: Introductionmentioning

confidence: 99%

Is there a Role for Genetics in Cardiac Calcification?

Hellman¹,

Mörner²,

Henein³

2019

ICFJ

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Calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischaemia, despite potential discrepancy in its expression pattern compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic aetiology for it. In a pilot study we studied three candidate genes, ENPP1, ABCC6 and NTE5 which may predispose to coronary arterial or valvular calcification. We studied 65 patients with CCAD and 5 patients with calcific aortic valve disease (CAVD). Five DNA variants potentially affecting protein function were found in six patients. Our findings support genetic variants might influence the development of CCAD and CAVD, however, segregation in the families must first be performed to ascertain any damaging effect of these variants. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes.

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Genetic variants in cardiac calcification in Northern Sweden

Cited by 3 publications

References 26 publications

Mild Ocular Findings and Skeletal Anomalies Producing a Marfanoid Appearance, Along with Autoimmune/Inflammatory Findings Due to SNV of Unknown Significance in Genes ABCC6 and OPA1 Inherited from the Mother

Mild Ocular Findings and Skeletal Anomalies Producing a Marfanoid Appearance, Along with Autoimmune/Inflammatory Findings Due to SNV of Unknown Significance in Genes ABCC6 and OPA1 Inherited from the Mother

A Novel Idiopathic Atrial Calcification: Pathologic Manifestations and Potential Mechanism

Is there a Role for Genetics in Cardiac Calcification?

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