Compound heterozygous variants in MAPK8IP3 were detected in severe congenital hypotonia mimicking lethal spinal muscular atrophy.

Mitogen-activated protein kinase 8-interacting protein 3 gene (MAPK8IP3) encodes the c-Jun-amino-terminal kinase-interacting protein 3 (JIP3) and is involved in retrograde axonal transport. Heterozygous de novo pathogenic variants in MAPK8IP3 result in a neurodevelopmental disorder with or without brain abnormalities and possible axonal peripheral neuropathy. Whole-exome sequencing was performed on an individual presenting with severe congenital muscle hypotonia of neuronal origin mimicking lethal spinal muscular atrophy.

Helsmoortel-Van der Aa Syndrome-Cardiothoracic and Ectodermal Manifestations in Two Patients as Further Support of a Previous Observation on Phenotypic Overlap with RASopathies.

The -gene-related neurodevelopmental disorder Helsmoortel-Van der Aa syndrome is a rare syndromic-intellectual disability-an autism spectrum disorder first described by Helsmoortel and Van der Aa in 2014. Recently, a large cohort including 78 patients and their detailed phenotypes were presented by Van Dijck et al., 2019, who reported developmental delay, speech delay and autism spectrum disorder as nearly constant findings with or without variable cardiological, gastroenterological, urogenital, endocrine and neurological manifestations.

[Genetic revision of the Hungarian Cystic Fibrosis Registry].

Introduction: Cystic fibrosis (CF) is one of the most common monogenic diseases. Genetic testing is becoming increasingly reasoned to establish or confirm the diagnosis by detecting abnormal mutations.

Objective: In order to develop a diagnostic strategy for cystic fibrosis and to facilitate mutation-specific treatments, the genetic revision of the Hungarian Cystic Fibrosis Registry was performed.

Cytogenetic Investigation of Infertile Patients in Hungary: A 10-Year Retrospective Study.

Chromosome abnormalities play a crucial role in reproductive failure. The presence of numerical or structural aberrations may induce recurrent pregnancy loss or primary infertility. The main purpose of our study was to determine the types and frequency of chromosomal aberrations in infertile patients and to compare the frequency of structural aberrations to a control group.

Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.

We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.

-related intellectual disability due to paternal germinal mosaicism.

The -related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common forms of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the gene by deletions, duplications, or sequence variants has been identified as deleterious.

22q13 Microduplication Syndrome in Siblings with Mild Clinical Phenotype: Broadening the Clinical and Behavioral Spectrum.

Distal duplication 22q (22q13.3qter) is a rare condition with only 24 cases described so far. Parental balanced reciprocal translocations and pericentric inversions involving chromosome 22 predispose to the conception of an unbalanced offspring and are more frequently reported than de novo events.

Clinical and genetic characteristics of craniosynostosis in Hungary.

Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied.

Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation.

Pfeiffer syndrome is an autosomal dominant disorder classically characterized by craniosynostosis, facial dysmorphism and limb anomalies. The majority of cases are caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. A specific, rare mutation p.

[Results of clinical and genetic diagnosis of rare diseases in the Eastern region of Hungary (2007-2013)].

Introduction: 80% of rare diseases have a genetic origin, and 50% manifest themselves as congenital anomalies. Their adequate health care includes early recognition of genetic anomalies and prevention of recurrence.

Aim: The aims of the authors were to provide correct diagnoses to patients with multiple congenital anomalies with or without mental retardation attending to the outpatient clinic of the Clinical Genetics Center at the University of Debrecen in the time interval between August 1, 2007 and March 31, 2013, establish the possibility of prenatal diagnosis, assess the distribution of different genetic mechanisms in the background of rare genetic diseases, compare them with international data, and develop an algorithm for the diagnostic approach of rare genetic diseases applicable in Hungary.

[Clinical and genetic characteristics of craniosynostosis].

Craniosynostosis is caused by premature fusion of one or more cranial sutures leading to deformity of the cranium. Depending on the type and number of the sutures involved and the order of their fusion, different forms of deformities may develop. Two main types of craniosynostosis can be distinguished: non-syndromic (isolated) and syndromic forms.

Achondroplasia with multiple-suture craniosynostosis: a report of a new case of this rare association.

We report on a female patient with an exceedingly rare combination of achondroplasia and multiple-suture craniosynostosis. Besides the specific features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and squamosal sutures was found. Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly.

New mutations in the ATM gene and clinical data of 25 AT patients.

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage.

Jumping translocation of chromosome 1q associated with good clinical outcome in a case of Burkitt leukemia.

Acquired jumping translocations (JTs) are rare secondary aberrations occurring in various hematological malignancies. In Burkitt lymphoma/leukemia (BL) chromosome 1q abnormalities such as partial or whole arm duplications/translocations are frequently associated with the disease-specific t(8;14)(q24;q32). JTs of 1q are considered to have a bad prognostic impact in BL.

Blepharophimosis mental retardation syndrome Say-Barber/Biesecker/Young-Simpson type - new findings with neuroimaging.

We report on a female patient with blepharophimosis mental retardation syndrome of Say/Barber/Biesecker/Young-Simpson (SBBYS) type. Main findings in her were marked developmental delay, blepharophimosis, ptosis, cleft palate, external auditory canal stenosis, small and malformed teeth, hypothyroidism, hearing impairment, and joint limitations. We performed diffusion tensor magnetic resonance imaging (MRI) and tractography of the brain which showed inappropriate myelination and disturbed white matter integrity.

[Detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation].

Subtelomeric regions of chromosomes are rich in genes; their rearrangements cannot be identified by traditional chromosome analysis. Since these subtelomeric aberrations are responsible for about 7% of cases with mental retardation, their detection is important both from the diagnostic point of view and to prevent recurrence in the family. Subtelomeric chromosomal alterations can be detected by fluorescence in situ hybridization.

[Expression of ZEBRA protein of Epstein-Barr virus in Hungarian patients with Hodgkin lymphoma: latent or lytic cycle?].

Introduction: Epstein-Barr virus is a ubiquitous human herpes virus in the Hungarian population. The virus is associated with an increasing number of lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of the virus to establish life-long persistent infection and induce growth transformation is related to the viral proteins that are variously expressed in both normal and malignant cells.

Association between the Epstein-Barr virus and Hodgkin's lymphoma in the North-Eastern part of Hungary: effects on therapy and survival.

This retrospective study included 109 patients with Hodgkin's lymphoma (HL; 45 females, 64 males). In 47 of the 109 HL patients (43%), immunohistochemical analysis of their formalin-fixed, paraffin-embedded histologic samples revealed Epstein-Barr virus (EBV) by latent membrane protein (LMP) 1. The highest virus association (50%) was found with the mixed cellularity histologic subtype, especially in patients aged 11-20 and >50 years.

IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in control subjects but does not explain elevated plasma IL-10 observed in Sjögren's syndrome in a Hungarian cohort.

The aim of this study was to investigate the frequency of the -1082 polymorphism of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian primary Sjögren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy volunteers were examined. Samples were analysed by the PCR restriction fragment length polymorphism method, and IL-10 plasma levels were assessed by a commercial enzyme-linked immunosorbent assay.

[Association of Hodgkin lymphoma with Epstein-Barr virus in Hungary].

Introduction: The occurrence of Epstein-Barr virus associated Hodgkin's lymphoma shows considerable variation from continent to continent and from country to country but in Hungary no such investigations have been performed so far.

Aim: The authors analyse the presence of Epstein-Barr virus and the type of latency in histologic samples taken from Hodgkin's disease patients.

Method: They have analyzed the presence of virus using PCR, in situ hybridisation and immunohistochemistry.

Single nucleotide polymorphisms: aging and diseases.

Differences of more than 3 million nucleotides can bee seen comparing the genomes of two individuals as a result of single nucleotide polymorphism (SNP). More and more SNPs can be identified and it seems that these alterations are behind of several biological phenomena. Personal differences in these nucleotides result for example in elevated disease susceptibilities, that is, certain nucleotides are more frequent in patients suffering from different diseases comparing to the healthy population.

On the role of aging in the etiology of autoimmunity.

Several types of diseases, among others autoimmune illnesses, could be coupled with the general processes of aging. The two-edged sword of immune defense is directed on one side against environmental attacks and on the other against the body itself. However, one has to make a difference between normal (physiological) clearance and autoimmune diseases, although both sides of autoimmunity are influenced by the general processes of senescence.

UVB light and 17-beta-estradiol have different effects on the mRNA expression of Ro/SSA and La/SSB autoantigens in HaCaT cells.

Antibodies produced against the Ro/SSA and La/SSB autoantigens are not only of diagnostic value but they may even play a role in the pathogenesis of several autoimmune diseases (Sjögren's syndrome, subacute cutaneous lupus erythematosus, neonatal lupus erythematosus and systemic lupus erythematosus). Among other factors, ultraviolet (UV) radiation and also the hormonal milieu are well-known cofactors in the pathogenesis of these autoimmune diseases. The goal of our research was to study the possible alterations in mRNA levels of three different Ro antigens and that of two La species produced by alternative splicing in transformed human keratinocytes (HaCaT cells) after UVB irradiation and after 17-beta-estradiol treatment.

[Detection and diagnostic value of t(14;18) translocation in minimal residual disease of follicular lymphoma].

The minimal residual disease is important in several malignant diseases, such as in hematopoietic malignancies (e.g. in follicular lymphoma) or in solid tumors, due to the presence of a tumor burden following a treatment of these diseases.