Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in Mucinous Lung Cell Carcinomas

Background: Invasive mucinous lung adenocarcinomas are rare and account for 2%–10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a weaker expression in mucinous adenocarcinomas compared with TTF1, but such correlation is still poorly researched

Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome

Congenital cataracts, facial dysmorphism, neuropathy (CCFDN) syndrome is a complex autosomal recessive multisystem disorder. The aim of the current study is to evaluate the degree of cognitive impairment in a cohort of 22 CCFDN patients and its correlation with patients’ age, motor disability, ataxia, and neuroimaging changes. Twenty-two patients with genetically confirmed diagnosis of CCFDN underwent a detailed neurological examination. Verbal and nonverbal intelligence, memory, executive functions, and verbal fluency wеre assessed in all the patients aged 4 to 47 years. Brain magnetic resonance imaging was performed in 20 affected patients. Eighteen affected were classified as having mild intellectual deficit, whereas 4 had borderline intelligence. In all psychometric tests, evaluating different cognitive domains, CCFDN patients had statistically significant lower scores when compared to the healthy control group. All cognitive domains seemed equally affected. The main abnormalities on brain MRI found in 19/20 patients included diffuse cerebral atrophy, enlargement of the lateral ventricles, and focal lesions in the subcortical white matter, different in number and size, consistent with demyelination more pronounced in the older CCFDN patients. The correlation analysis of the structural brain changes and the cognitive impairment found a statistically significant correlation only between the impairment of short-term verbal memory and the MRI changes

Molecular screening for fragile X syndrome in children with unexplained intellectual disability and/or autistic behaviour

Introduction: Fragile X syndrome (FXS, OMIM #300624) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. Aim: To present our experience with selective screening for FXS among high-risk children with intellectual disability/developmental delay/autistic behaviour and to further prove the importance of performing selective screening in a high-risk population. Materials and methods: Fifty-two children (45 boys and 7 girls) hospitalized in pediatric clinics or referred to genetic counseling services were tested with triplet repeat primed PCR based commercial kit. The mean age of participants was 6 years (the youngest was 2 years old, the oldest - 15 years old). These patients were selected based on the presence of at least one of the following clinical features: developmental delay, intellectual disability, and autistic-like behaviour. Results: All patients presented with developmental delay, including language delay. Intellectual disability and autistic-like behaviour were the most consistent features. Thirty-three children (63.4%) were with intellectual disability. Autism and autistic-like behaviour were observed in 22 patients (42.3%). Only 9 male patients (17.3%) presented with dysmorphic features typical for FXS. Three boys (5.7%) were found to be affected and two of their mothers - premutation carriers. Conclusions: The present study is the first attempt for molecular genetic selective screening for FXS among high-risk groups in north-eastern Bulgaria. Screening for FXS helps in making a definitive diagnosis along with providing genetic counseling to the family which includes reproductive planning and risk assessment

Molecular screening for fragile X syndrome in children with unexplained intellectual disability and/or autistic behaviour

Introduction: Fragile X syndrome (FXS, OMIM #300624) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. Aim: To present our experience with selective screening for FXS among high-risk children with intellectual disability/developmental delay/autistic behaviour and to further prove the importance of performing selective screening in a high-risk population. Materials and methods: Fifty-two children (45 boys and 7 girls) hospitalized in pediatric clinics or referred to genetic counseling services were tested with triplet repeat primed PCR based commercial kit. The mean age of participants was 6 years (the youngest was 2 years old, the oldest - 15 years old). These patients were selected based on the presence of at least one of the following clinical features: developmental delay, intellectual disability, and autistic-like behaviour. Results: All patients presented with developmental delay, including language delay. Intellectual disability and autistic-like behaviour were the most consistent features. Thirty-three children (63.4%) were with intellectual disability. Autism and autistic-like behaviour were observed in 22 patients (42.3%). Only 9 male patients (17.3%) presented with dysmorphic features typical for FXS. Three boys (5.7%) were found to be affected and two of their mothers - premutation carriers. Conclusions: The present study is the first attempt for molecular genetic selective screening for FXS among high-risk groups in north-eastern Bulgaria. Screening for FXS helps in making a definitive diagnosis along with providing genetic counseling to the family which includes reproductive planning and risk assessment

EGFR mutation status yield from bronchoalveolar lavage in patients with primary pulmonary adenocarcinoma compared to a venous blood sample and tissue biopsy

Background In recent years, there has been a revolution in the genomic profiling and molecular typing of lung cancer. A key oncogene is the epidermal growth factor receptor (EGFR). The gold standard for determining EGFR mutation status is tissue biopsy, where a histological specimen is taken by a bronchoscopic or surgical method (transbronchial biopsy, forceps biopsy, etc.). However, in clinical practice the tissue sample is often insufficient for morphological and molecular analysis. Bronchoalveolar lavage is a validated diagnostic method for pathogenic infections in the lower respiratory tract, yet its diagnostic value for oncogenic mutation testing in lung cancer has not been extensively investigated. This study aims to compare the prevalence of EGFR mutation status in bronchoalveolar lavage and peripheral blood referring to the gold standard - tissue biopsy in patients with primary lung adenocarcinoma. Methods Twenty-six patients with adenocarcinoma were examined for EGFR mutation from tissue biopsy, peripheral blood sample and bronchoalveolar lavage. Results Thirteen patients had wild type EGFR and the other 13 had EGFR mutation. EGFR mutation from a peripheral blood sample was identified in 38.5% (5/13) of patients, whereas EGFR mutation obtained from bronchoalveolar lavage (BAL) was identified in 92.3% (12/13). This study demonstrates that a liquid biopsy sample for EGFR status from BAL has a higher sensitivity compared to a venous blood sample

GNE myopathy in Roma patients homozygous for the p.I618T founder mutation

GNE myopathy is an autosomal-recessive disorder caused by mutations in the GNE gene, encoding the key enzyme in the sialic acid biosynthetic pathway, UDP-N-acetylglucosamine 2-epimerase/N-acetyl mannosamine kinase. We studied 50 Bulgarian Roma patients homozygous for p.I618T, an ancient founder mutation in the kinase domain of the GNE gene, dating before the Gypsy exodus from North West India. The clinical features in the Bulgarian ONE group can be described with disease onset mostly in the third decade, but in individual cases, onset was as early as 10 years of age. The majority of patients had foot drop as the first symptom, but three patients developed hand weakness first. Muscle weakness was early and severe for the tibialis anterior, and minimal or late for quadriceps femoris, and respiratory muscles were only subclinically affected even in the advanced stages of the disease. During a 15-year follow-up period, 32 patients became non-ambulant. The average period between disease onset and loss of ambulation was 10.34 +/- 4.31 years, ranging from 3 to 20 years. Our analysis of affected sib pairs suggested a possible role of genetic modifying factors, accounting for significant variation in disease severity. (C) 2015 Elsevier B.V. All rights reserved