Complex phenotypes in metabolic muscle diseases

Vladutiu, Georgirene D.

doi:10.1002/1097-4598(200008)23:8<1157::aid-mus1>3.0.co;2-o

Cited by 16 publications

(3 citation statements)

References 16 publications

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“…In these cases, a new clinical phenotype may be produced that is not characteristic of any of the contributing single‐gene defects when they are present alone. Therefore, when complex phenotypes with atypical features are observed in cases of metabolic myopathies (e.g., earlier onset or increased severity of symptoms), it is prudent to test for a panel of suspected disorders 55…”

Section: Inheritance Of Metabolic Myopathiesmentioning

confidence: 99%

Laboratory diagnosis of metabolic myopathies

Vladutiu

2002

Muscle and Nerve

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The metabolic myopathies are a heterogeneous group of disorders inherited by a variety of modes that include gene defects in both the nuclear and mitochondrial genomes. Many factors impact on the expression of the pathogenic mutations that cause these disorders including genetic background, environmental factors, and coexisting disorders. Molecular technology has greatly improved the ability to make definitive diagnoses in many of the metabolic myopathies in the last decade and particularly has demonstrated that the wide diversity in the severity of mutations contributes to understanding genotype-phenotype correlations. In some cases, molecular testing obviates the necessity to perform an invasive muscle biopsy. However, it is also clear that the diagnostic yield from molecular testing is incomplete and particularly low among the mitochondrial myopathies as a group, ranging from approximately 6% to 19% in well-classified high-risk groups. Therefore, it is often essential to combine clinical, biochemical, histopathologic, and molecular data for each patient in order to arrive at a definitive diagnosis. The approach to the laboratory diagnosis of metabolic myopathies is described emphasizing both noninvasive and invasive testing, highlighting the molecular methodologies with the benefits and disadvantages of each technology, and documenting how to determine whether patients have coexisting disorders.

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Section: Inheritance Of Metabolic Myopathiesmentioning

confidence: 99%

Laboratory diagnosis of metabolic myopathies

Vladutiu

2002

Muscle and Nerve

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“…We are also learning that the phenotypes of even simple Mendelian disorders are influenced by complex genetic and environmental factors. [48][49][50][51] The observations that genotypes rarely predict phenotypes absolutely have significant ramifications for counseling. We must recognize that for single-gene disorders with high penetrance, the information derived from such testing may be relatively easy to interpret and apply.…”

Section: Predictive Genetic Testingmentioning

confidence: 99%

Changing Public Demand in the Genetic Counseling during the Past Decades

Papp

2011

Donald School Journal of Ultrasound in Obstetrics and Gynecology

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Before discovering genetic rules, genetic counseling was based on empirical observations. In this process, it was important to recognize that certain diagnoses were more frequent in certain couples’ descendants. The 20th century witnessed revolutionary progress in the science of genetics that coincided with increasing societal demands and therefore became an integral part of modern genetic counseling. Genetic screening is changing from Mendelian disease ascertainment to predictive testing. We are also learning that the phenotypes of even simple Mendelian disorders are influenced by complex genetic and environmental factors. Moreover, developing knowledge about genotype/phenotype associations and many other aspects of genetic epidemiology will increasingly require referral to clinical geneticists.

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“…These cases are remarkable in that concomitant reductions have been identified in more than one enzyme involved in four different energy metabolism pathways including fatty acid b-oxidation, oxidative phosphorylation, glycogenolysis, and highenergy phosphate recycling. Thus, the co-existence of multiple single-gene mutations in an individual appears to have resulted in complex phenotypes characterized by the emergence of symptoms atypical of the heterozygote state of any of the individual underlying disorders (Vladutiu 2000(Vladutiu , 2001. Indeed, symptoms in these patients have not been directly predictable on the basis of the individual defects.…”

Section: Complex Phenotypes and Iemsmentioning

confidence: 99%

Metabolism as a complex genetic trait, a systems biology approach: Implications for inborn errors of metabolism and clinical diseases

Vockley

2008

J of Inher Metab Disea

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Summary Multifactorial and polygenic inheritance is commonly recognized for many genetic conditions including physical anomalies, complex congenital malformation syndromes, and even common disorders such as adult-onset diabetes mellitus. It has only recently been suggested as a mechanism for inheritance in inborn errors of metabolism. This article reviews the phenomenon of multiple partial enzyme deficiencies leading to clinical relevant biochemical derangements (synergistic heterozygosity) and its implications for other more common disorders such as diabetes and obesity.

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Complex phenotypes in metabolic muscle diseases

Cited by 16 publications

References 16 publications

Laboratory diagnosis of metabolic myopathies

Laboratory diagnosis of metabolic myopathies

Changing Public Demand in the Genetic Counseling during the Past Decades

Metabolism as a complex genetic trait, a systems biology approach: Implications for inborn errors of metabolism and clinical diseases

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