Primary antibody deficiencies in Turkey: molecular and clinical aspects

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

     

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects

Immunologic Research -     

Protracted febrile myalgia syndrome in familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal, recessively inherited multisystem disease that affects various groups of people originating from the Mediterranean Sea region, most specifically those of Jewish, Turkish, Armenian, and Arabic ethnicity. Recurrent attacks of fever and sterile polyserositis of the peritoneum, synovial membranes, and pleura are the main clinical features, although the clinical features of FMF have been expanded in recent years to also include severe myalgia, scrotal swelling, cardiac involvement, and protracted febrile myalgia syndrome (PFMS). PFMS is seen in only a small percentage of FMF patients and is characterized by severe debilitating myalgia of the upper and lower extremities and high fever, occasionally accompanied by abdominal pain, diarrhea, arthritis/arthralgia, and transient vasculitic purpura mimicking Henoch-Schönlein purpura (HSP). Here, we report on a patient with FMF who also presents with PFMS, which is an uncommon and severe manifestation of the disease.     

Case report: seizures in a child caused by a large venous angioma

Cerebral venous angioma is a congenital anomaly of the medullary vein, the vessel that drains into the transparenchymal venous stem. This lesion is also referred to as a developmental venous anomaly. A few reports in the literature have documented developmental venous anomaly-related epilepsy, neurologic deficits, and intracranial hemorrhage. A 3-year-old boy was referred to our hospital after he sustained an afebrile, tonic-clonic, focal seizure of 15 minutes' duration that affected his right arm, leg, and eyebrow. Cerebral digital subtraction angiography showed a bilateral, large periventricular developmental venous anomaly. This report describes the clinical and radiologic findings for this large venous angioma that caused seizures in a child.     

Novel mutation in the PANK2 gene leads to pantothenate kinase-associated neurodegeneration in a Pakistani family

Pantothenate kinase-associated neurodegeneration is an autosomal-recessive disorder associated with the accumulation of iron in the basal ganglia. The disease presents with dystonia, rigidity, and gait impairment, leading to restriction of activities and loss of ambulation. The disorder is caused by defective iron metabolism associated with mutations in the PANK2 gene, which codes for the pantothenate kinase enzyme. We report on a mutation screen conducted in two siblings to establish a molecular diagnosis of the disease and a genetic test for the family.     

Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study

INTRODUCTION: One hypothesis that unifies the diversity of symptoms associated with schizophrenia involves the disruption of connectivity between brain regions. As white matter provides rapid and efficient communication between brain regions, this study was initiated to assess the early disruption of white matter pathways in children and adolescent with schizophrenia. MATERIALS AND METHODS: Diffusion tensor images were acquired on 14 children and adolescents with schizophrenia, one subject with schizoaffective disorder, and 15 age and gender matched controls. The DTI images were acquired in twelve directions on a 3 T Siemens Trio scanner. The images were transformed into fractional anisotropy and mean diffusivity maps and a group analysis was performed using SPM2. RESULTS: Children and adolescent patients with schizophrenia demonstrated a significant decrease in FA and associated increase in AD in the left posterior hippocampus (p<0.001, Bonferroni corrected on the cluster-level). These diffusion differences were not statistically significant when IQ was used as a covariate in the analysis. DISCUSSION: These findings suggest hippocampal white matter abnormalities that present early in the development of schizophrenia. The lack of significant differences when IQ is used as a covariate suggests that this hippocampal region is associated with cognitive changes associated with schizophrenia.     

Value of a negative colonoscopy in patients with non-specific gastrointestinal symptoms

BACKGROUND: The yield of colonoscopy for neoplasia among patients aged <50 years with non-specific gastrointestinal symptoms is very low. However, a negative colonoscopy may benefit these patients by decreasing anxiety and thereby reducing subsequent health resource utilization. This study sought to characterize the effect of a negative colonoscopy in terms of: (i) reassurance value; and (ii) decreasing health resource utilization, in patients under 50 years of age with non-specific gastrointestinal symptoms (abdominal pain, diarrhea, constipation). METHODS: Consecutive patients, aged 18-49 years, undergoing their first colonoscopy for evaluation of non-specific gastrointestinal symptoms (abdominal pain, diarrhea, constipation) were prospectively enrolled. Health-related anxiety was evaluated before and immediately after disclosure of the negative result of colonoscopy using a validated questionnaire and at 1-, 2- and 6-month intervals postcolonoscopy by telephone follow-up. Symptom scores and health resource utilization were assessed prior to colonoscopy and at 2 and 6 months postcolonoscopy. RESULTS: Fifty-nine patients were prospectively enrolled. Mean health anxiety score declined immediately after colonoscopy from 20.6 to 17.8. Sustained improvement was seen in anxiety scores at 1, 2 and 6 months. Symptom scores also decreased at 6 months for abdominal pain (2.3 to 1.5), diarrhea (2.3 to 1.6) and constipation (1.9 to 1.6). There was a significant decrease in all four measures of health resource utilization at 6 months postcolonoscopy. CONCLUSIONS: Despite minimal diagnostic yield, colonoscopy for non-specific gastrointestinal symptoms in patients <50 years of age is associated with a decline in health-related anxiety and symptom scores. These effects appear to translate into reductions in health resource utilization.