Aortic disease and cardiomyopathy in patients with a novel DNMT3A gene variant causing Tatton-Brown-Rahman syndrome.

Tatton-Brown-Rahman syndrome (TBRS) is a rare congenital genetic disorder caused by autosomal dominant pathogenic variants in the DNA methyltransferase DNMT3A gene. Typical TBRS clinical features are overgrowth, intellectual disability, and minor facial anomalies. However, since the syndrome was first described in 2014, a widening spectrum of abnormalities is being described.

Molecular and Functional Characterisation of a Novel Intragenic 12q24.21 Deletion Resulting in Haploinsufficiency Syndrome.

Heterozygous pathogenic variants in the gene cause impaired intellectual development and distinctive facial features with or without cardiac defects (MIM #616789). This complex neurodevelopmental disorder is characterised by various phenotypic features, including plagiocephaly, strabismus, clubfoot, poor speech, and developmental delay. The aim of this study was to evaluate the clinical significance and consequences of a novel heterozygous intragenic deletion in a proband with clinical features of a -related disorder through extensive clinical, molecular, and functional characterisation.

The PHF21A neurodevelopmental disorder: an evaluation of clinical data from 13 patients.

Potocki-Shaffer syndrome (PSS) is a rare neurodevelopmental disorder caused by deletions involving the 11p11.2-p12 region, encompassing the plant homeodomain finger protein 21A (PHF21A) gene. PHF21A has an important role in epigenetic regulation and PHF21A variants have previously been associated with a specific disorder that, whilst sharing some features of PSS, has notable differences.

PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation.

Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1.

Donor Splice Site Variant in Causes Christianson Syndrome in a Lithuanian Family: A Case Report.

Background and Objectives: The pathogenic variants of SLC9A6 are a known cause of a rare, X-linked neurological disorder called Christianson syndrome (CS). The main characteristics of CS are developmental delay, intellectual disability, and neurological findings. This study investigated the genetic basis and explored the molecular changes that led to CS in two male siblings presenting with intellectual disability, epilepsy, behavioural problems, gastrointestinal dysfunction, poor height, and weight gain.

Compound heterozygous c.598_612del and c.1746-20C > G CAPN3 genotype cause autosomal recessive limb-girdle muscular dystrophy-1: a case report.

Background: Autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1), also known as calpainopathy, is a genetically heterogeneous disorder characterised by progression of muscle weakness. Homozygous or compound heterozygous variants in the CAPN3 gene are known genetic causes of this condition. The aim of this study was to confirm the molecular consequences of the CAPN3 variant NG_008660.

Two Novel Variants in Genes of Arrhythmogenic Right Ventricular Cardiomyopathy - a Case Report.

Summary Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy, characterized by fibrofatty replacement of myocytes in the right ventricular, left ventricular or both ventricles. It is caused by pathogenic variants of genes encoding desmosomal (, , , , and non-desmosomal proteins, and is one of the most common causes of sudden cardiac death in young athletes. Therefore, early identification, correct prevention and treatment can prevent adverse outcomes.

Aborted Cardiac Arrest in LQT2 Related to Novel () Variant Identified in One Lithuanian Family.

Congenital long QT syndrome (LQTS) is a hereditary ion channelopathy associated with ventricular arrhythmia and sudden cardiac death starting from young age due to prolonged cardiac repolarization, which is represented by QT interval changes in electrocardiogram (ECG). Mutations in human ether-à-go-go related gene ( (7q36.1), formerly named ) are responsible for Long QT syndrome type 2 (LQT2).

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.

Genome Editing in Medicine: Tools and Challenges.

Studies which seek fundamental, thorough knowledge of biological processes, and continuous advancement in natural sciences and biotechnology enable the establishment of molecular strategies and tools to treat disorders caused by genetic mutations. Over the years biological therapy evolved from using stem cells and viral vectors to RNA therapy and testing different genome editing tools as promising gene therapy agents. These genome editing technologies (Zinc finger nucleases, TAL effector nucleases), specifically CRISPR-Cas system, revolutionized the field of genetic engineering and is widely applied to create cell and animal models for various hereditary, infectious human diseases and cancer, to analyze and understand the molecular and cellular base of pathogenesis, to find potential drug/treatment targets, to eliminate pathogenic DNA changes in various medical conditions and to create future "precise medication".

A de novo 13q31.3 microduplication encompassing the miR-17 ~ 92 cluster results in features mirroring those associated with Feingold syndrome 2.

Hemizygosity of the MIR17HG gene encoding the miR-17 ~ 92 cluster is associated with Feingold syndrome 2 characterized by intellectual disability, skeletal abnormalities, short stature, and microcephaly. Here, we report on a female with a de novo 13q31.3 microduplication encompassing MIR17HG but excluding GPC5.

Etiological profile of hearing loss amongst Lithuanian pediatric cochlear implant users.

Introduction: Congenital sensorineural hearing loss is a heterogeneous disorder; its etiological profile varies between populations. Pathogenic variants of GJB2 gene are the major cause of non-syndromic hearing loss. Congenital cytomegalovirus infection (cCMV) is the most important prenatal etiological factor causing hearing loss and other disorders.

Autosomal recessive hypercholesterolemia: Case report.

Introduction: Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is a very rare monogenic disorder affecting less than 1 in 1000,000 people and is characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), leading to aggressive and premature atherosclerotic cardiovascular disease if left untreated. Lowering of LDL-C is the main target of the treatment. We report on a 29-year-old male patient born in nonconsanguineous Lithuanian family homo(hemi-)zygous for LDLRAP1 gene variant causing ARH.

De novo splice site variant of ARID1B associated with pathogenesis of Coffin-Siris syndrome.

Background: Coffin-Siris syndrome is an extremely rare syndrome associated with developmental and congenital anomalies. It is caused by heterozygous pathogenic variants of ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, and SOX11.

Methods: This case study presents the whole exome sequencing of a patient with characteristic clinical features of Coffin-Siris syndrome.

Novel GLI3 variant causes Greig cephalopolysyndactyly syndrome in three generations of a Lithuanian family.

Background: Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS).

Methods And Results: Sequencing analysis of the GLI3 coding region identified a novel donor splice site variant NC_000007.

A novel CHD7 variant disrupting acceptor splice site in a patient with mild features of CHARGE syndrome: a case report.

Background: CHARGE syndrome (MIM# 214800)-which is characterised by a number of congenital anomalies including coloboma, ear anomalies, deafness, facial anomalies, heart defects, atresia choanae, genital hypoplasia, growth retardation, and developmental delay-is caused by a heterozygous variant in the CHD7 (MIM# 608892) gene located on chromosome 8q12. We report the identification of a novel c.5535-1G > A variant in CHD7 and provide the evaluation of its effect on pre-mRNA splicing.

Opposite chromosome constitutions due to a familial translocation t(1;21)(q43;q22) in 2 cousins with development delay and congenital anomalies: A case report.

Rationale: Chromosomal rearrangements are the major cause of multiple congenital abnormalities and intellectual disability.

Patient Concerns And Diagnosis: We report 2 first cousins with unbalanced chromosomal aberrations of chromosomes 1 and 21, resulting from balanced familial translocation. Chromosome microarray analysis revealed 8.

Recurrent fetal syndromic spina bifida associated with 3q26.1-qter duplication and 5p13.33-pter deletion due to familial balanced rearrangement.

Objective: Neural tube defects belong to the second most common group of congenital anomalies, after heart defects, which can be diagnosed by prenatal ultrasonography. Rarely, neural tube defects can be associated with chromosomal abnormalities, including full and partial aneuploidies. We report a familial fetal case with syndromic spina bifida and discuss its association with partial 3q duplication and partial 5p deletion.

The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population.

Background: Congenital hearing loss (CHL) is diagnosed in 1 - 2 newborns in 1000, genetic factors contribute to two thirds of CHL cases in industrialised countries. Mutations of the GJB2 gene located in the DFNB1 locus (13q11-12) are a major cause of CHL worldwide. The aim of this cross-sectional study was to assess the contribution of the DFNB1 locus containing the GJB2 and GJB6 genes in the development of early onset hearing loss in the affected group of participants, to determine the population-specific mutational profile and DFNB1-related HL burden in Lithuanian population.

Thiamine responsive megaloblastic anemia syndrome: a novel homozygous SLC19A2 gene mutation identified.

Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare autosomal recessive disorder especially in countries where consanguinity is uncommon. Three main features are characteristic of the disease - megaloblastic anemia, early onset deafness, and non-type I diabetes. TRMAS is a Mendelian disorder; a gene SLC19A2 coding high affinity thiamine transporter mediating vitamin B1 uptake through cell membrane has been identified.

Age-dependent heterogeneity of familiar hypertrophic cardiomyopathy phenotype: a role of cardiovascular magnetic resonance.

In this case report, we present familiar hypertrophic cardiomyopathy with age-dependent heterogeneity of the disease phenotype among the members of one family who carry the same mutation of the myosin-binding protein C gene. Phenotypic heterogeneity is common in patients with familial forms of hypertrophic cardiomyopathy, both in clinical expression and outcome. Compared with other noninvasive cardiac imaging modalities, cardiovascular magnetic resonance provides an opportunity to more accurately characterize the varying phenotypic presentations of hypertrophic cardiomyopathy.