Molecular genetic study of acute intermittent porphyria in Russia: <i>HMBS</i> gene mutation spectrum and problem of penetrance

Goncharova, Maria; Pshenichnikova, O. S.; Luchinina, Yulia; Pustovoit, Yaroslav; Карпова, И. В.; Surin, V. L.

doi:10.1111/cge.13558

Cited by 8 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The low penetrance of AIP and the significant difference between the penetrance found in families with AIP and that found in the general population indicate that AIP susceptibility is affected by the inheritance of HMBS gene mutation as well as other genetic or environmental factors. A hypothesis has been put forth that AIP inheritance does not follow the classical autosomal dominant pattern but an oligogenic or polygenic inheritance pattern with environmental modifiers (25,58,74,75).…”

Section: Modifying Genesmentioning

confidence: 99%

“…Currently, a few defects in genes regulating the nervous system (UNC13A, ALG8, FBXO38, AGRN, DOK7, and SCN4A) have been detected in a study in Russia (58). The latter three genes are related to congenital myasthenic syndrome (CMS), whose symptoms bear a remarkable resemblance to neurologic features of AIP attacks.…”

Section: Some Genes Regulating the Nervous Systemmentioning

confidence: 99%

“…The latter three genes are related to congenital myasthenic syndrome (CMS), whose symptoms bear a remarkable resemblance to neurologic features of AIP attacks. Thus, the combination of a mutation in the HMBS gene with defects in genes regulating the nervous system may play a key role in triggering acute AIP attacks and prompting the development of specific symptomatic traits (58). However, this assumption needs to be verified in future studies.…”

Section: Some Genes Regulating the Nervous Systemmentioning

confidence: 99%

See 2 more Smart Citations

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Tian

Peng

et al. 2020

IRDR

View full text Add to dashboard Cite

Acute intermittent porphyria (AIP) is a dominant inherited disorder with a low penetrance that is caused by mutations in the gene coding for hydroxymethylbilane synthase (HMBS). Information about the epidemiology and molecular genetic features of this rare disorder is crucial to clinical research, and particularly to the evaluation of new treatments. Variations in the prevalence and penetrance of AIP in various studies may due to the different inclusion criteria and methods of assessment. Here, the prevalence and penetrance of AIP are analyzed systematically, and the genetic traits of different populations and findings regarding the genotype-phenotype correlation are summarized. In addition, quite a few studies have indicated that AIP susceptibility was affected by other factors, such as modifying genes. Findings regarding possible modifying genes are documented here, helping to reveal the pathogenesis of and treatments for AIP. The status of research on AIP in China reveals the lack of epidemiological and genetic studies of the Chinese population, a situation that needs to be promptly remedied.

show abstract

Section: Modifying Genesmentioning

confidence: 99%

Section: Some Genes Regulating the Nervous Systemmentioning

confidence: 99%

Section: Some Genes Regulating the Nervous Systemmentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Tian

Peng

et al. 2020

IRDR

View full text Add to dashboard Cite

show abstract

“…AIP manifestation is very complicated and is likely affected by other factors not studied in this study; differences in other genes or genetic factors can be the cause of the difference in metabolites between asymptomatic carriers and patients. Molecular genetic studies using whole-exome sequencing have shown that mutations carriers of both the HMBS gene and the ALAD gene may not necessarily affect AIP clinical manifestation, and mutations in genes regulating nervous system genes contributed to AIP manifestation [25]. Studies investigating possible contribution of mutations in genes regulating AIP manifestation and metabolites is warranted; however, they would require a larger sample of AIP patients and their asymptomatic relatives.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers

Lin

Shiao

Cheng

et al. 2021

Cells

View full text Add to dashboard Cite

This study aims to present the serum metabolite profiles of patients with acute intermittent porphyria (AIP) and identify specific metabolites that could potentially discriminate between AIP, asymptomatic HMBS mutation carriers, and healthy individuals. The study cohort included 46 female participants: 21 AIP patients, 5 asymptomatic carriers, and 20 ‘normal’ participants (without HMBS gene mutation). Serum samples were analyzed for 157 selected metabolites or clinical variables using an assay combining liquid chromatography MS/MS and direct flow injection. AUC analysis was used to distinguish unique variables between the three groups. A total of 15 variables differed significantly between the AIP and normal control group (VIP score > 1.0 and p < 0.05 with FDR correction). In AIP patients, the levels tyrosine, valine, and eGFR were significantly lower, and the levels of sphingomyelin C16:0, C24:0, C24:1, phosphatidylcholine diacyl C32:1, C36:1, C36:3, ornithine, sarcosine, citrulline, blood urea nitrogen AST, and ALT were significantly higher. The AUC of these 15 variables in discriminating between normal and AIP patients ranged between 0.73 and 0.94 (p < 0.05). In conclusion, serum metabolic profiles differ between normal individuals and patients carrying the HMBS mutation. The unique metabolites associated with AIP identified in this study may be useful for monitoring the development of AIP symptoms.

show abstract

“…Moreover, we do not know why some individuals (primarily women) suffer from recurrent attacks. Only one whole exome sequencing has been carried out in porphyria patients thus far, however [ 30 ]. Last but not least, it is not known which genetic and environmental factors contribute to the different penetrance of the acute porphyrias from individual to individual [ 31 ].…”

Section: General Aspects (Introduction)mentioning

confidence: 99%

Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know

Petrides

2022

Diagnostics

View full text Add to dashboard Cite

Heme, iron protoporphyrin IX, is one of life’s most central molecules. Hence, availability of the enzymatic machinery necessary for its synthesis is crucial for every cell. Consequently, inborn errors of porphyrin metabolism that compromise normal synthesis, namely the family of porphyrias, undermine normal cellular metabolism given that heme has functions in catalytic centers, signal transduction and functional regulation and its synthesis is fully integrated into the center of intermediary metabolism. Very often, diagnosis of porphyrias is difficult and therefore delayed. Therapy can be as complicated. Over the last 50 years, several strategies have been developed: because of its integration with other parts of intermediary metabolism, the infusion of glucose (glucose effect) was one of the first attempts to counterbalance the dysregulation of porphyrin synthesis in porphyrias. Since heme synthesis is impaired, infusional replacement of heme was the next important therapeutic step. Recently, siRNA technology has been introduced in order to downregulate 5-ALA-synthase 1, which contributes to the patho-physiology of these diseases. Moreover, other novel therapies using enzyme protein replacement, mRNA techniques or proteostasis regulators are being developed.

show abstract

Molecular genetic study of acute intermittent porphyria in Russia: HMBS gene mutation spectrum and problem of penetrance

Cited by 8 publications

References 15 publications

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers

Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know

Contact Info

Product

Resources

About