Institute of Mother and Child (IMC), founded in 1948, is a unique institution providing medical care for women, children, and the entire family. IMC is concerned with complex aspects of healthcare including clinical, epidemiological, and fundamental investigations. Our mission is also organization and professional surveillance of health services and postgraduate training related to this field. The Institute comprises of clinical research departments, research laboratories, a multi-disciplinary in-patient and out-patient clinics and technical services.
The Department of Medical Genetics has been founded in 1973 as one of the first such scientific and diagnostic centers in Poland. The clinical and research work of the Department has focused on the diagnostics of inherited disorders, genetic counselling and investigation of the nature of cytogenetic and molecular defects in genetic conditions. The diagnostic and research activities are implemented in genetic counselling, cytogenetics and molecular units.
We implement modern molecular methods into diagnostics and research to provide our patients with the most reliable genetic services based on the latest knowledge. Our professional abilities and high quality standards are documented by annual successful participation in several international quality programs (i.e. British NEQAS EMQN, CF NETWORK). The Department is a reference center certified in training professionals in the field of clinical and laboratory medical genetics.
The Genetic Counselling Unit operates as an outpatient service and offers the diagnosis and care of genetically determined syndromes and genetic counselling for genetic risk families (including genetic risk assessment and screening in order to identify person at risk for genetic disorders). Diagnostic activities focus on clinical diagnostics and genetic counselling for families affected with congenital malformations, dysmorphic syndromes, isolated and syndromic mental retardation, autism spectrum disorders, neurogenetic diseases, imprinting disorders, RAS-MAPK pathway disorders, craniosynostoses, CFTR-related disorders, genodermatoses, some of the metabolic diseases and genomic disorders (microdeletion/microduplication syndromes) and reproductive disorders. The research concern work on the diseases pathogenesis and correlation between clinical symptoms and genotype. Genetic Counselling Unit conducted comprehensive pre- and postnatal diagnostics and genetic counselling (including prenatal diagnosis for genetic risk families and pregnancies with suspicion of fetal malformations in fetal ultrasonography/MRI). Its experience and skills are based on over 35 000 families currently registered in our Genetic Counselling Unit patient’s database. Medical doctors working at the genetic Counselling Unit are specialists in clinical genetics and most of them have Ph.D degree in this field. They are among the most experienced dysmorphologists and clinical geneticists in Poland. Some of them have additional specializations in other fields of medicine, e.g. pediatrics, neurology or prenatal ultrasonography. The qualifications of the Genetic Counselling team are constantly improved through participation in courses and conferences, as well as through personal contacts and cooperation with various centers both domestic and foreign.
The Cytogenetic Unit provides comprehensive services in all types of constitutional chromosome analysis in postnatal and prenatal cases. These studies include both traditional cytogenetic techniques as well as the new methods of molecular cytogenetics. Molecular cytogenetic analyses by fluorescence in situ hybridisation (FISH) with commercially available probes are offered in several applications such as recognition of prenatal aneuploidy, microdeletion/microduplication syndromes or identification of marker chromosomes. The laboratory have significant experience with FISH technique utilizing home-made bacterial probes for identification of structural chromosomal aberrations. In 2004, the array Comparative Genomic Hybridization (aCGH) was implemented into research projects and subsequently for postnatal and prenatal diagnosis. The main focus of our diagnostic and research activities is a better understanding of the molecular mechanisms and phenotypic consequences of submicroscopic genomic rearrangements. The efforts of the research facility focus on mapping genes involved in the pathogenesis of intellectual disability, autism spectrum disorders, epilepsy and heart defects using the latest technology of molecular cytogenetics. We are particularly interested in determining potential phenotypic consequences of copy number variation and elucidation of the role of genomic architectural in genomic instability.
The Molecular Genetics Unit concentrates on the diagnostic and research aspects of inherited disorders. On the grounds of vast experience in this field our center has been indicated as a reference for clinical and molecular diagnosis of several genetic diseases. The main aim of research activities in the Inherited Diseases Diagnostics Laboratory involve investigation of molecular pathogenesis of cystic fibrosis (CF), chronic pancreatitis, genodermatoses (mainly epidermolysis bullosa and ichthyosis), hearing loss, infertility and metabolic disorders. The aim of this studies is to get insight into natural history of the disease, to identify molecular defects and get further knowledge concerning genotype-phenotype correlations, as well as to find novel genes, which are involved in pathogenesis of those diseases. In order to achieve those goals, we use DNA and RNA next generation sequencing, as well as functional in vitro analysis. As a result of these activities, we have developed dedicated diagnostic panels for the analysis of genes related to chronic pancreatitis, genodermatoses, hearing loss, infertility and metabolic disorders. Pathogenesis of diseases regulated by epigenetic mechanisms and characteristics of developmental disturbances such as growth alterations, intellectual disability and behavioral problems (especially in Prader-Willi syndrome, Angelman syndrome, Beckwith–Wiedemann syndrome and Silver-Russel syndrome) are investigated by the team in the Developmental Genetics Laboratory. Other research and diagnostics in this Laboratory are focused on disorders related to developmental abnormalities. One of the main areas of interest are RASopathies – multisystemic disorders caused by mutations in genes encoding proteins involved in RAS/MAPK signalling pathway. Primarily, we focused our research on Noonan syndrome – the application of molecular techniques such as next generation sequencing, led us to identify new variants or new genes related to the disease pathogenesis. We also aim to explore the molecular background of another RASopathy – neurofibromatosis type I. As a result of our research, we have developed a gene panel for RASopaties diagnosis with next generation sequencing. We have also developed a dedicated panel for the analysis of genes related to disturbances of suture formation (craniosynostoses) and growth alterations (overgrowth and short stature). Another research topic of Developmental Genetics Laboratory is related to our experience as a reference laboratory for fragile X syndrome diagnosis. In male patients with familial intellectual disability that were negative for the FMR1 gene mutation, we looked for genes related to X-linked intellectual disability (XLID). In 50% of the examined families, we identified the molecular defect responsible for the disease, including new variants in known ID genes and variants in genes suspected to be involved in intellectual functioning. As a continuum, functional studies based on induced pluripotent stem cells (iPSC) derived from mature somatic cells of the patient are held. Induced pluripotent stem cells can be generated from skin fibroblasts or peripheral blood mononuclear cells (PBMCs) by genetic reprogramming. They can differentiate into any of the three germ layers, including nerve cells, and represent an applicable patient-specific cellular model to study the monogenic form of intellectual disability. We are also a reference laboratory for spinal muscular atrophy (SMA) diagnosis. Besides the assessment of SMN1 and SMN2 copy number, the analysis of the SMN1 gene for the presence of point mutations as well as genes related to other types of SMA is offered. Together with Neuromuscular Unit of Mossakowski Medical Research Centre, PAS, we are involved in the research project that aims to explain the genetic causes of floppy child syndrome with special attention to neuromuscular disorders. Neurogenetics Laboratory studies the influence of genes and gene expression on the development of neurological disorders in children and adults but also provide the diagnostic evaluation of neurogenetic disorders for patients and their families. The team uses powerful modern genomic technologies, including next generation sequencing, to identify changes in genes that cause disease but also cell biology and disease modeling approaches in investigation of the basis of diseases. The main interest of this laboratory concentrates on studying neurodevelopmental disorders (NDDs), especially epileptic encephalopathies and encephalopathies with epilepsy. We focus our research on identification and characterization of molecular background of those disorders but also their genetic and phenotypic heterogeneity. These studies also lead to interest in the issues of the molecular basis of intellectual disability and autism, common comorbidities of epilepsy in NDDs, but also neuronal migration disorder, which may present all those symptoms. The other studies in Neurogenetic Laboratory include developmental age diseases such as Friedreich’s ataxia or Pelizeaus-Merzbacher disease and dystonias. The work does not focus only on developmental age, in cooperation with the Medical University of Warsaw, research is carried out on the basis of neurodegenerative diseases such as Parkinson’s disease, but also atypical parkinsonism, both in terms of analysis of already known genes and identification new ones. The Cell Biology Laboratory research group investigates the molecular and cellular pathophysiology of human genetic diseases, with special emphasis on neurodevelopmental and neurodegenerative disorders associated with abnormal brain development and protein aggregation, such as neuronal migration diseases with microcephaly, leukodystrophies and genetically based leukoencephalopathies, Huntington’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. The aim of these studies is to understand basic brain biology and also to elucidate the function of protein aggregates under pathological conditions. In addition to the above topics, we are studying the structure and function of proteins implicated in the pathogenesis of torsion dystonia type 1, spinal muscular atrophy and cystic fibrosis.
Aside from understanding and characterisation of molecular and cytogenetic pathology of numerous diseases, a practical effect of dozens of research projects (both completed and ongoing) is the introduction of the most recent cytogenetic and molecular biology methods into routine diagnostics and genetic counseling of inherited conditions.