Mitochondrial DNA deletion and duplication in Kearns–Sayre Syndrome (KSS) with initial presentation as Pearson Marrow‐Pancreas Syndrome (PMPS): Two case reports in Barranquilla, Colombia

Sabella-Jiménez, Vanessa; Otero-Herrera, Carlos; Silvera-Redondo, Carlos; Garavito-Galofre, Pilar

doi:10.1002/mgg3.1509

Cited by 11 publications

(6 citation statements)

References 72 publications

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“…Another study suggested that as low amounts as 1 ng of DNA sample should be used for MLPA reaction to get higher sensitivity (Mayorga et al, 2016). Although several authors reported successfully identified deletions (Liu et al, 2021) and duplications (Sabella‐Jiménez et al, 2020) using MLPA method, in our case, the results of the test were negative using different DNA dilutions. Conversely, long‐range PCR method detected heteroplasmic deletion using two different pairs of PCR primers.…”

Section: Discussioncontrasting

confidence: 65%

“…Single large‐scale deletions of mtDNA are usually identified in the blood DNA samples for the patients with Kearns‐Sayre syndrome. Deletions vary in size and location on the mitochondrial genome in different individuals, although the most reported deletion (NC_012920.1:m.8470_13446del4977), is identified in more than a third of patients with KSS and involves 4977 bp and 12 mitochondrial genes (Sabella‐Jiménez et al, 2020; Shemesh & Margolin, 2018). The molecular investigation revealed novel de novo 5888 bp mtDNA deletion (NC_012920.1:m.6069_11956del) for our patient.…”

Section: Discussionmentioning

confidence: 99%

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Kearns‐Sayre syndrome case. Novel 5,9 kb mtDNA deletion

Grigalionienė

Burnytė

Balkelienė

et al. 2022

Molec Gen & Gen Med

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Background Kearns‐Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder characterized by onset before 20 years of age and a typical clinical triad: progressive external ophthalmoplegia, pigmentary retinopathy and cardiac conduction anomalies. In most cases KSS is caused by spontaneous heteroplasmic single large‐scale mitochondrial DNA (mtDNA) deletions. Long‐range polymerase chain reaction (LR‐PCR), next generation sequencing (NGS) and multiplex ligation‐dependent probe amplification (MLPA) are the most widely applied methods for the identification of mtDNA deletions. Here, we report the case of 20‐year‐old male who presented with classic Kearns‐Sayre syndrome, confirmed by novel 5,9 kb mtDNA deletion. Methods and results LR‐PCR and MLPA methods were applied to identify the mitochondrial DNA deletion for the patient, but the results were conflicting. Molecular analysis using primer walking and Sanger sequencing identified a novel 5888 base pairs mtDNA deletion (NC_012920.1:m.6069_11956del) with CAAC nucleotides repeat sequence at the breakpoints. Conclusion Our study enriched the mtDNA variation spectrum associated with KSS and demonstrated the importance of choosing relevant molecular genetic methods.

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Section: Discussioncontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Kearns‐Sayre syndrome case. Novel 5,9 kb mtDNA deletion

Grigalionienė

Burnytė

Balkelienė

et al. 2022

Molec Gen & Gen Med

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“…48,53 While many patients with PMPS do not survive infancy due to multisystem derangements, those who do survive with hematological management and supportive care transition to a Kearns-Sayre syndrome (KSS) diagnosis in childhood or adolescence. 48,52,[54][55][56][57] Improvement in bone marrow, pancreatic, hepatic, and renal parameters over time in PMPS may be explained by the frequent division of cells in these organs, allowing for selection against cells with mitochondrial DNA deletions, while the transition to a more predominantly myopathic phenotype reflects the post-mitotic state of skeletal muscle and accumulation of mitochondrial DNA deletions in myocytes over time. 52…”

Section: Pearson Marrow-pancreas Syndromementioning

confidence: 99%

Hereditary myopathies associated with hematological abnormalities

2022

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The diagnostic evaluation of a patient with suspected hereditary muscle disease can be challenging. Clinicians rely largely on clinical history and examination features, with additional serological, electrodiagnostic, radiologic, histopathologic, and genetic investigations assisting in definitive diagnosis. Hematological testing is inexpensive and widely available, but frequently overlooked in the hereditary myopathy evaluation. Hematological abnormalities are infrequently encountered in this setting; however, their presence provides a valuable clue, helps refine the differential diagnosis, tailors further investigation, and assists interpretation of variants of uncertain significance. A diverse spectrum of hematological abnormalities is associated with hereditary myopathies, including anemias, leukocyte abnormalities, and thrombocytopenia.Recurrent rhabdomyolysis in certain glycolytic enzymopathies co-occurs with hemolytic anemia, often chronic and mild in phosphofructokinase and phosphoglycerate kinase deficiencies, or acute and fever-associated in aldolase-A and triosephosphate isomerase deficiency. Sideroblastic anemia, commonly severe, accompanies congenital-to-childhood onset mitochondrial myopathies including Pearson marrowpancreas syndrome and mitochondrial myopathy, lactic acidosis, and sideroblastic anemia phenotypes. Congenital megaloblastic macrocytic anemia and mitochondrial dysfunction characterize SFXN4-related myopathy. Neutropenia, chronic or cyclical, with recurrent infections, infantile-to-childhood onset skeletal myopathy and cardiomyopathy are typical of Barth syndrome, while chronic neutropenia without infection occurs rarely in DNM2-centronuclear myopathy. Peripheral eosinophilia may accompany eosinophilic inflammation in recessive calpainopathy. Lipid accumulation in leukocytes on peripheral blood smear (Jordans' anomaly) is pathognomonic for neutral lipid storage diseases. Mild thrombocytopenia occurs in autosomal dominant, childhood-onset STIM1 tubular aggregate myopathy, STIM1 and ORAI1 deficiency syndromes, and GNE myopathy. Herein, we review these hereditary myopathies in which hematological features play a prominent role.

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“…In autopsy specimens, parathyroid glands are atrophic or even absent ( 96 ). Yet, in more recent reports, hypomagnesemia, which is commonly associated with hypoparathyroidism from suppression and/or impaired function of parathyroid hormone, has been described in few case reports ( 97 , 98 ).…”

Section: Clinical Features Of Mitochondrial Disease—endocrinementioning

confidence: 99%

Endocrine Manifestations and New Developments in Mitochondrial Disease

Lim

Panagiotou

et al. 2021

Endocrine Reviews

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Mitochondrial diseases are a group of common inherited diseases causing disruption of oxidative phosphorylation. Some patients with mitochondrial disease have endocrine manifestations, with diabetes being predominant but also include hypogonadism, hypoadrenalism and hypoparathyroidism. There have been major developments in mitochondrial disease over the last decade that have major implications for all patients. The collection of large cohorts of patients has better defined the phenotype of mitochondrial diseases and the majority of patients with endocrine abnormalities have involvement of several other systems. This means that patients with mitochondrial disease and endocrine manifestations need specialist follow up because some of the other manifestations, such as stroke-like episodes and cardiomyopathy, are potentially life threatening. Also, the development and follow up of large cohorts of patients means that there are clinical guidelines for the management of patients with mitochondrial disease. There is also considerable research activity to identify novel therapies for the treatment of mitochondrial disease. The revolution in genetics, with the introduction of next generation sequencing, has made genetic testing more available and establishing a precise genetic diagnosis is important since it will affect the risk for involvement for different organ systems. Establishing a genetic diagnosis is also crucial since there are important reproductive options have been developed which will prevent the transmission of mitochondrial disease due to mitochondrial DNA variants to the next generation.

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Mitochondrial DNA deletion and duplication in Kearns–Sayre Syndrome (KSS) with initial presentation as Pearson Marrow‐Pancreas Syndrome (PMPS): Two case reports in Barranquilla, Colombia

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 72 publications

Kearns‐Sayre syndrome case. Novel 5,9 kb mtDNA deletion

Kearns‐Sayre syndrome case. Novel 5,9 kb mtDNA deletion

Hereditary myopathies associated with hematological abnormalities

Endocrine Manifestations and New Developments in Mitochondrial Disease

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