The Genetic and Molecular Basis of Human Diseases

Prof. Ing. Stanislav Kmoch, CSc.

Prof. Ing. Stanislav Kmoch, CSc. — Project head

1st Faculty of Medicine of the Charles University

About us

The group studies the pathology and physiology of purine metabolism, especially de novo purine synthesis (DNPS). Currently, the group’s research focuses on the preparation and determination of DNPS metabolites and capturing new, as yet undescribed disorders in a population of patients with neurological impairments that have not yet been diagnosed. We also specialize in the study of the purinosome, the multi-protein complex DNPS enzymes. Our goal is to prepare a model system for in vivo study of the dynamic formation of purinosome and the molecular changes in physiological and pathological conditions.

Research Areas:

  • Genetics, genomics and molekular biology


Research Objectives:

  • Identification of the genetic basis of various human phenotypes (mostly pathologies)
  • Functional characterization of identified genetic variants (mutations) and their products
  • Identification of pathophysiologic processes related to individual genetic defects
  • Contribution of identified genes and their variants to complex phenotypes
  • Definition of diagnostic markers and therapeutic targets
  • Development of methods and protocol(s) for assessment of eventual treatment efficacy


Content of the Research:

Formerly, this project was called Molecular Pathology of Defects of the Haem and Haemoprotein Synthesis and was focused on the pathological disorders of the synthesis of haem and haemoproteins. Its research objectives were:

1) Description of the availability of clinical material and basic methods of the research

2) To study the molecular basis of defects of the haem metabolism to determine the impact of the reduced availability of haem on the biogenesis of mitochondria. Haem metabolon in relation to changes of the availability of haem (haemoproteins)

3) To characterize and describe individual inborn defects in the biosynthetic pathway of haem.


Recently, the group has been focused on the characterisation of the genetic, genomic and molecular basis of rare Mendelian diseases, on the characterisation of the role of rare genetic variants in complex diseases and the definition of novel diagnostic markers and therapeutic targets. Historically, these projects were based on gynotyping, linkage analysis, candidate gene sequencing and gene expression studies. Curently, all all these projects are based on a combination of genome/exome sequencing, copy-number analysis, gene expression studies and detailed biochemical, molecular and the histopathologic characterisation of clinical materials and cellular models of individual diseases. The majority of these projects have been initiated by clinicians or biomedical researchers from various departments of the First and Second Faculty of Medicine of Charles University and affiliated university hospitals. Over the last several years, the capacity is being increasingly used in projects initiated by external users from the entire Czech Republic and abroad.




Zikanova M., Krijt J., Skopova V., Krijt M., Baresova V., Kmoch S. 2015. Screening for adenylosuccinate lyase deficiency using tandem mass spectrometry analysis of succinylpurines in neonatal dried blood. Clin Biochem, 48: 2-7

Jurecka A., Zikanova M., Kmoch S., Tylki-Szymanska A. 2015. Adenylosuccinate lyase deficiency. J Inherit Metab Dis, 38: 231-42


Jurecka A, Zikanova M, Jurkiewicz E, Tylki-Szymanska A. 2014. Attenuated adenylosuccinate lyase deficiency: a report of one case and a review of the literature. Neuropediatrics 45:50-55.


Krijt J, Skopova V, Adamkova V, Cermakova R, Jurecka A, Kmoch S, Zikanova M. 2013. The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. Clin Biochem 46:1899-1901.

Duval N, Luhrs K, Wilkinson TG, 2nd, Baresova V, Skopova V, Kmoch S, Vacano GN, Zikanova M, Patterson D. 2013. Genetic and metabolomic analysis of AdeD and AdeI mutants of de novo purine biosynthesis: cellular models of de novo purine biosynthesis deficiency disorders. Mol Genet Metab 108(3):178-89.


Baresova V, Skopova V, Sikora J, Patterson D, Sovova J, Zikanova M, Kmoch S. 2012. Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency. Hum Mol Genet 21(7):1534-43.


Vliet LK, Wilkinson TG, 2nd, Duval N, Vacano G, Graham C, Zikanova M, Skopova V, Baresova V, Hnizda A, Kmoch S and others. 2011. Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency. Mol Genet Metab 102(1):61-8.


Zidkova L, Krijt J, Sladkova J, Hlobilkova A, Magner M, Zikanova M, Kmoch S, Friedecky D, Zeman J, Elleder M and others. 2010. Oligodendroglia from ADSL-deficient patient produce SAICAribotide and SAMP. Mol Genet Metab 101(2-3):286-8.


Prof. Ing. Stanislav Kmoch, CSc. Prof. Ing. Stanislav Kmoch, CSc.

Prof. Ing.
Stanislav Kmoch, CSc.

Head of Program Development of Diagnostic and Therapeutic Procedures, Head of Group Genetic and Molecular Basis of Human Diseases
Ing. Marie Zikánová, Ph.D. Ing. Marie Zikánová, Ph.D.

Marie Zikánová, Ph.D.

Study of purine metabolism disorders, Genetic and Molecular Basis of Human Diseases