Diagnosis of malignant hyperthermia: a comparison of the in vitro contracture test with the molecular genetic diagnosis in a large pedigree.

Background For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients. Methods The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion. Results Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation. Conclusions In families with known MH mutations, there is a 50% chance of reliably confirming MH susceptibility by noninvasive testing. The authors found the negative predictive value of genetic testing to be 0.95 (95% confidence interval, 0.75-0.99), but for patient safety, they still recommend following the guidelines for genetic testing in MH and therefore performing an IVCT in case of negative genetic results.

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A Comparison of the Caffeine Halothane Muscle Contracture Test with the Molecular Genetic Diagnosis of Malignant Hyperthermia

Anesthesiology ◽

10.1097/00000542-199107000-00002 ◽

1991 ◽

Vol 75 (1) ◽

pp. 4-8 ◽

Cited By ~ 16

Author(s):

Alex E. MacKenzie ◽

Gregory Allen ◽

Donelda Lahey ◽

Mary-Lou Crossan ◽

Kevin Nolan ◽

...

Keyword(s):

Malignant Hyperthermia ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Muscle Contracture ◽

Molecular Genetic Diagnosis

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Molecular genetic diagnosis and genotype-phenotype correlations in children and adolescents with recurrent fractures

Bone Abstracts ◽

10.1530/boneabs.7.p116 ◽

2019 ◽

Author(s):

Gigante Jessica Del ◽

Craig Munns ◽

Andrew Biggin

Keyword(s):

Children And Adolescents ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Molecular Genetic Diagnosis

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Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0433 ◽

2020 ◽

Vol 33 (6) ◽

pp. 691-701 ◽

Cited By ~ 1

Author(s):

Tatsushi Tanaka ◽

Kohei Aoyama ◽

Atsushi Suzuki ◽

Shinji Saitoh ◽

Haruo Mizuno

Keyword(s):

Congenital Hypothyroidism ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Japanese Patients ◽

Thyroid Stimulating Hormone ◽

Allelic Variant ◽

Genetic Investigation ◽

Pathogenic Variants ◽

Recessive Genes ◽

Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

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Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Diabetologia ◽

10.1007/s00125-008-0942-y ◽

2008 ◽

Vol 51 (4) ◽

pp. 546-553 ◽

Cited By ~ 250

Author(s):

S. Ellard ◽

C. Bellanné-Chantelot ◽

A. T. Hattersley ◽

Keyword(s):

Practice Guidelines ◽

Best Practice ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Maturity Onset Diabetes ◽

Best Practice Guidelines ◽

Onset Diabetes ◽

Molecular Genetic Diagnosis

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Ectodermal Dysplasia: Thoughts and Practical Concepts Concerning Disease Classification - The Role of Functional Pathways in the Molecular Genetic Diagnosis

Dermatology ◽

10.1159/000346613 ◽

2013 ◽

Vol 226 (2) ◽

pp. 111-114 ◽

Cited By ~ 7

Author(s):

Peter H. Itin

Keyword(s):

Ectodermal Dysplasia ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Disease Classification ◽

Molecular Genetic Diagnosis ◽

Functional Pathways

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Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples

The Lancet ◽

10.1016/0140-6736(91)92981-7 ◽

1991 ◽

Vol 337 (8753) ◽

pp. 1311-1313 ◽

Cited By ~ 135

Author(s):

S.R. Hammans ◽

M.G. Sweeney ◽

M. Brockington ◽

J.A. Morgan-Hughes ◽

A.E. Harding

Keyword(s):

Molecular Genetic ◽

Genetic Diagnosis ◽

Blood Samples ◽

Molecular Genetic Diagnosis

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Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test

British Journal of Anaesthesia ◽

10.1093/bja/aew047 ◽

2016 ◽

Vol 116 (4) ◽

pp. 566-568 ◽

Cited By ~ 18

Author(s):

N Roux-Buisson ◽

N Monnier ◽

E Sagui ◽

A Abriat ◽

C Brosset ◽

...

Keyword(s):

Malignant Hyperthermia ◽

Ryanodine Receptor ◽

Positive Response ◽

Heat Stroke ◽

Receptor Type ◽

Exertional Heat Stroke ◽

In Vitro Contracture Test

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Clinician's modern approaches to molecular genetic diagnosis of glioblastomas

Problems in oncology ◽

10.37469/0507-3758-2021-67-1-13-19 ◽

2021 ◽

Vol 67 (1) ◽

pp. 13-19

Author(s):

Turna Ashkhatcava ◽

Marina Tatarinova ◽

Lali Kogoniya ◽

David Naskhletashvili ◽

Vadim Zhukov

Keyword(s):

Braf Mutation ◽

Molecular Mechanisms ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Braf V600e ◽

Poor Prognostic Factor ◽

Molecular Genetic Diagnosis ◽

The Brain ◽

Tert Mutation ◽

Primary Glioblastomas

The article is devoted to the issue of molecular genetic diagnosis of cerebral glioblastomas. Despite significant advances in neurooncology, little progress has been made in prolonging the life of patients with cerebral glioblastoma, and a significant part of the effectiveness of treatment depends on the recognition of two prognostic biomarkers: mutations of the isocitrate dehydrogenase (IDH) promoter and the methylation of the O6-methylguanine methyl transferase (MGMT) promoter. The article summarizes the data of world and domestic clinical studies, allowing to supplement the histological characteristics of primary glioblastomas with genetic markers: the presence of the TERT mutation, EFGR amplification, loss of PTEN function, LOH 10q, and the presence of the BRAF mutation. It should be noted that the amplification of EGFR, causing resistance to apoptotic stimuli and alkylating chemotherapy with Temozolomide, attracts much attention as a therapeutic target. The frequency of occurrence of the TERT mutation is 90% of all tumors of various genesis, most often the TERT mutation is found in oligodendroglioma or primary glioblastoma. Loss of heterozygosity in the region of localization of the PTEN gene is observed in many types of sporadic tumors, including more than 40% of glioblastomas. Mutations in this gene are found in tumors of the brain, endometrium, prostate, kidney, and mammary gland. The presence of a PTEN mutation is a poor prognostic factor. LOH 22q is much more common in secondary glioblastomas (82%) than in primary glioblastomas (41%). Among brain tumors, the BRAF mutation is most common with pleomorphic xanastrocytoma (60-70%).The BRAF V600E mutation was found in epithelioid glioblastoma, which is a rare and aggressive type of glioblastoma, characterized by an unfavorable prognosis (about 6 months) and frequent leptomeningeal spread. Thus, knowledge of the molecular mechanisms of carcinogenesis will enable a personalized approach to treatment with glioblastomas of the brain.

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