Fenilketonurija sergančių vaikų emocijų ir elgesio problemos

Phenylketonuria (PKU) is an inherited genetic metabolic disorder in which the enzyme required to digest phenylanine (Phe) is missing. If untreated, individuals with PKU will develop high levels of Phe in their blood which can affect brain development and function. That's why low protein diet must be introduced as early as possible from the birth. Nevertheless, several studies show higher incidence of behavioral problems, especially internalizing, in early treated PKU children. Parental maladjustment to their child's chronic illness and everyday stress related to the burden of special diet can be reasons for psychological problems of PKU children. The aim of our study is to evaluate the psychological adjustment of PKU children (as compared to healthy controls) and analyze it in the context of psychological impact of PKU on the family.Parents of 37 early-treated PKU children (age 4-14 years old) and of 37 matched controls answered the Child Behavior Checklist (CBCL, Achenbach, 1991) and questionnaire on stress coping strategies (Elklit, 1996). Parents of PKU children also answered the questionnaire on reactions to child's disease and it's impact on the family.The results of present study indicate that PKU children have significantly more behavioral problems than healthy controls. They are more withdrawn, anxious /depressive, aggressive, have more social and attention problems. The higher rates of internalizing and overall problems are related to parental maladjustment (feelings of guilty and anger) together with maladaptive (emotional) everyday stress coping strategies. Two latter factors further indulging the child, that also predicts the psychological maladjustment of PKU children.Ankstyvas ir tinkamas fenilketonurijos gydymas yra būtinas norint užtikrinti normalią psichinę ir fizinę šia liga sergančių vaikų raidą. Net tinkamai gydomi fenilketonurija sergantys vaikai turi elgesio problemų, tiesiogiai nekylančių dėl pačios ligos. Mūsų tyrimo tikslas buvo įvertinti fenilketonurija sergančių ir nuo jos gydomų vaikų elgesio problemas ir tai, kaip jos susijusios su psichologiniu ligos poveikiu šeimai bei tai, kaip tėvai reagavo į vaiko ligą, kokie yra jų santykiai su sergančiu vaiku. Tyrimo rezultatai parodė, kad sergantys fenilketonurija vaikai turi daugiau emocijų ir elgesio problemų nei sveiki jų bendraamžiai. Patikimiausiai fenilketonurija sergančių vaikų internalios, socialinės ir dėmesio bei visos emocijų ir elgesio problemos siejosi su mamų reagavimu į vaiko ligą kaltės ir pykčio jausmais, į emocijas orientuotų streso įveikos strategijų naudojimu, nuolaidžiaujančiais santykiais su sergančiu vaiku

X-linked juvenile retinoschisis: phenotypic and genetic characterization

Juvenile X-linked retinoschisis (XLRS, MIM#312700) belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography (SD-OCT) images. The mean central foveal thickness was 569.7 µm. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio (T (p.R200L) mutation was detected in one case, showing to be pathogenic in silico analysis. c. (92_97) insC (p.W33fs) mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits

KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis.

Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kučinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract. Severe loss-of-function cases were incompatible with life, whereas those individuals with milder missense variants presented with severe global developmental delay, syndactyly of 2nd and 3rd toes, and severe muscle hypotonia resulting in incapacity to stand without support. Consistent with a causative role for KIAA1109 loss-of-function/hypomorphic variants in this syndrome, knockdowns of the zebrafish orthologous gene resulted in embryos with hydrocephaly and abnormally curved notochords and overall body shape, whereas published knockouts of the fruit fly and mouse orthologous genes resulted in lethality or severe neurological defects reminiscent of the probands' features.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Atvejo pristatymas: Jakobseno sindromas su nedideliu veido dismorfizmu, sunkiu klausos sutrikimu ir trombocitopenija

Background. Jacobsen syndrome is a rare syndrome with variable phenotypic expression depending on the breakpoints and the size of 11q deletion. There is presented a wide range of phenotypes of varying severity. Detailed molecular cytogenetic analysis leads to better knowledge of genetic causes of this syndrome. Materials and methods. Molecular cytogenetic analysis using subtelomeric FISH and array CGH was performed for a patient with Jacobsen syndrome. Results. Subtelomeric FISH detected an unbalanced translocation 46,XY,der(11)t(11;13)(q24.2;p11.2) of our patient. Array CGH analysis revealed a 13.95 Mb terminal deletion of the 11q23.3 region (breakpoint positions 120, 505, 418–134, 452, 384, NCBI build 36). FISH and GTG banding analysis identified a balanced translocation 46,XX,t(11;13) (q24.2;p11.2) of patient’s mother. Conclusions. The results of this case report suggest the need of combining both molecular cytogenetic methods: array CGH and FISH for precise analysis of patients with Jacobsen syndrome

Diagnostic significance of FNAB miRNA expression in papillary thyroid carcinoma

The aim of the study was to evaluate the diagnostic utility of specific miRNAs in the preoperative assessment of thyroid nodules. One hundred and sixty thyroid fine needle aspiration biopsy (FNAB) samples with suspected thyroid carcinoma were collected. To detect the levels of miRNA expression in FNAB, next generation small RNA sequencing was performed in 60 samples. Based on the results obtained, three miRNAs (miR125A, miR200B, miR4324) were selected for further analysis. Based on the most frequently reported miRNAs in the literature associated with thyroid papillary carcinoma (PTC), two more miRNA (miR146B, miR221) were selected for further validation, using real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 36 benign and 64 PTC samples. Expression of miR125A, miR146B, miR221, and miR4324 was significantly higher in patients with PTC compared with benign thyroid nodules (p ˂ 0.05). miR125A and miR4324 were also significantly more highly expressed in patients with extrathyroidal tumor extension compared to those without extrathyroidal PTC extension (p < 0.001). We also found a significantly higher expression of miR221 (p = 0.043) in patients with multifocal carcinomas compared to patients with single foci carcinomas. This prospective study showed that the expression analysis of four miRNAs (miR125A, miR146B, miR221, and miR4324) improve accuracy of FNAB, which could allow a better pre-operative diagnostic and prognostic assessment of thyroid malignancies

Genome rearrangements in neurodevelopmental disorders of the central nervous system: origins, genomic mechanisms, functional and clinical consequences. Review article

Intellectual disability affects about 1-2% of the general population worldwide, and this is the leading socio-economic problem of the healthcare system. Reasearch into the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Extensive molecular technologies are being used in research to determine the genetic causes of these conditions. In our research, the detection of chromosomal aberrations by molecular karyotyping and whole exome sequencing capable of uncovering pathogenic variants in any of the human genes were the main technologies used to identify the molecular causes of intellectual disability. Collaboration with foreign scientific institutions for further clinical, molecular and functional investigations of rare causes of intellectual disability has allowed the characterisation of rare known and new syndromes. We believe that new insights into the molecular causes and pathogenesis mechanisms of the intellectual disability may be useful in developing treatment options in the future

Acute pre-B lymphoblastic leukemia and congenital anomalies in a child with a de novo

Microdeletions and microduplications are recurrent in the q11.2 region of chromosome 22. The 22q11.2 duplication syndrome is an extremely variable disorder with a phenotype ranging from severe intellectual disability, facial dysmorphism, heart defects, and urogenital abnormalities to very mild symptoms. Both benign and malignant hematological entities are rare. A male patient was diagnosed with mild facial dysmorphia, congenital heart anomalies shortly after birth and acute bowel obstruction due to malrotation of the intestine at the age of 3 years. A whole-genome single nucleotide polymorphism (SNP) array revealed a de novo 6.6 Mb duplication in the 22q11.1q11.22 chromosomal region. A year later, the patient was diagnosed with acute pre-B lymphoblastic leukemia (pre-B ALL). Five genes, CDC45, CLTCL1, DGCR2, GP1BB and SEPT5, in the 22q11.1q11.22 region are potentially responsible for cell cycle division. We hypothesized that dosage imbalance of genes implicated in the rearrangement could have disrupted the balance between cell growth and differentiation and played a role in the initiation of malignancy with a hyperdiploid leukemic clone, whereas over-expression of the TBX1 gene might have been responsible for congenital heart defects and mild facial dysmorphi

A novel variant in the PDE4D gene is the cause of Acrodysostosis type 2 in a Lithuanian patient: a case report

Background: Acrodysostosis is a rare hereditary disorder described as a primary bone dysplasia with or without hormonal resistance. Pathogenic variants in the PRKAR1A and PDE4D genes are known genetic causes of this condition. The latter gene variants are more frequently identified in patients with midfacial and nasal hypoplasia and neurological involvement. The aim of our study was to analyse and confirm a genetic cause of acrodysostosis in a male patient. Case presentation: We report on a 29-year-old Lithuanian man diagnosed with acrodysostosis type 2. The characteristic phenotype includes specific skeletal abnormalities, facial dysostosis, mild intellectual disability and metabolic syndrome. Using patient’s DNA extracted from peripheral blood sample, the novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G > C was identified in the gene PDE4D via Sanger sequencing. This variant causes amino acid change (NP_001098101.1:p.(Arg194Pro)) in the functionally relevant upstream conserved region 1 domain of PDE4D. Conclusions: This report further expands the knowledge of the consequences of missense variants in PDE4D that affect the upstream conserved region 1 regulatory domain and indicates that pathogenic variants of the gene PDE4D play an important role in the pathogenesis mechanism of acrodysostosis type 2 without significant hormonal resistance