Student Researchers' Society Topics

Co-supervisor: Dr. SZALAI, Renáta

Co-supervisor: Dr. SZABÓ, András

The development of a significant part of rare genetic disorders can be traced back to changes in the copy number (for example deletions or duplications) of different dosage-sensitive regions of the genome. Array comparative genome hybridization (aCGH) plays an extremely important role in the investigation of these genetic/genomic disorders, enabling the high-resolution examination of the entire genome in one step. This technology can detect small genomic variations that could not be identified with traditional cytogenetic methods. aCGH is particularly useful in the diagnosis of rare diseases where the detection of copy number abnormalities can be crucial for proper diagnosis, treatment strategy and genetic counseling.

In our institute, since 2013, we have performed aCGH investigations for groups of patients with different clinical indications, during which we managed to establish the diagnosis in many patients after a successful genotype-phenotype correlation analysis.

During the project, a detailed examination of the genotype-phenotype correlation and a comparison of the clinical indications and genetic results would take place in these and additional patients.

Application of FISH compared to traditional banding techniques allows detecting deletions with 3-5 Mb (megabase) in size. Since the application of the method, so-called microdeletion syndromes became known, which are deletion of neighbouring genes on a chromosome (contacting genes syndrome). The affected people have “similar” phenotypic features because of the really similar deletion. The most known microdeletion syndromes are Prader-Willi, Angelman, Williams, Smith-Magenis syndrome and the DiGeorge syndrome. Henceforth diagnosis of many other similar diseases is taking place regularly in the laboratory of our institute.

Co-supervisor: Dr. TILL, Ágnes

Intellectual disability is one of the most common developmental disorder characterized by significant limitations in intellectual functioning and in adaptive behavior, as expressed in conceptual, social and practical adaptive skills. It is important to know the underlying genetic causes of the disease, thereby enabling to understand the pathology of the disease and to predict its prognosis. New generation techniques (whole exome sequencing, whole genome sequencing) bring science closer to understanding and recognizing the underlying causes of the diseases. During the work using these techniques we would evaluate the different molecular genetic alterations and compare them with the symptomatology and case history of the patients.

Co-supervisor: Dr. MAGRATH, Heléna

Infant muscular hypotonia is one of the more frequent referrals we come across at our Developmental Neurology Specialty Clinic. Telling apart central from peripheral hypotonia by meticulous anamnesis and thorough physical exam is usually the easy part. When it comes to the precise diagnosis, though, conventional blood tests, imaging and electrophysiological exams commonly fail and a molecular genetic test is warranted.

Therapeutic interventions are available for a handful of rare diseases which make early diagnosis ever so important.

Apart from learning to process clinical data of our patients diagnosed with muscular hypotonia, the students’ would get a hands-on experience of working in paediatric neurology as well as in molecular genetic diagnostics.

Co-supervisor: Dr. CZAKÓ, Márta

We gathered a lot of information about brain development as a result of the technical advancement of pre- and postnatal ultrasound, and MR examinations as well in the last decades. Besides this the knowledge about the genetic mechanisms and the regulating genes, gene networks of brain development raised as a result of the advancement of molecular genetic techniques.

The genetic alterations behind developmental disorders are heterogeneous, they can be monogenic faults, or copy number variations (CNVs).

When examining patients with intellectual disability and dysmorphia, we detected CNVs affecting brain development in several patients with aCGH, in our institute since 2013.

During the work, the patients’ genotype-phenotype correlation will be examined thoroughly.

Sclerosis tuberosa is a multisystemic disorder with an incidence of 1:6000-1:9000. The disease has autosomal dominant heredity, although it appears as a new mutation in most of the patients. Mutations in the genes TSC1 and TSC2 cause the disease. The examination of the 2 genes in Hungary are only available in our institute.

During the work, we would examine the symptomatology and case history of the patients and analyze the family anamnesis in correspondence with the detected mutation.

The symptoms of Dravet syndrome, also known as febrile seizure+ syndrome (GEFS+) shows a broad spectrum, thus the beginning of the disease can differ as well. The genetic background of this is disease associated with mutations in the SCN1A gene, which we can analyze in the institution in the last several years. During the work, we would evaluate the different molecular genetic alterations and compare them with the symptomatology and case history of the patients.

Our institute is involved in mitochondrial DNA diagnostics and research of mitochondrial DNA alterations in rare diseases since 1999. Mitochondrial diseases comprise a group of rare diseases with a very broad phenotypic presentation, including diseases with variable progression and with both childhood- and adult-onset presentation. The common mechanism underlying this disease group is a deficiency of energy-pathways either encoded by the mitochondrial DNA or the nuclear DNA. In recent years our department has been investigating the phenotypic and genotypic variability of MELAS-syndrome, the molecular background of Leigh-disease and the genetic elucidation of maternally inherited deafness. Our biobank of mitochondrial diseases comprising more than 400 samples is an excellent source for the study of phenotype-and genotype variability in mitochondrial diseases. We primarily aim to attract students with a clinical focus also interested in the laboratory background behind diseases.