Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Multiple sulfatase deficiency: A case series of four children

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.Key Words: Child, multiple sulfatase deficiency, sulfatase-modifying factor 1 gene     

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.     

Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy

Journal of Neurology - Oxaliplatin-induced neuropathy (OIN) implies axonal damage of both small and large sensory nerve fibers. We aimed at comparing the neurophysiological changes occurred after...     

Association of cholesterol 7α-hydroxylase (CYP7A1) promoter polymorphism (rs3808607) and cholesterol 24S-hydroxylase (CYP46A1) intron 2 polymorphism (rs754203) with serum lipids,vitamin D levels,and multiple sclerosis risk in the Turkish population

Neurological Sciences - Patients with multiple sclerosis (MS) have significantly lower vitamin D levels. Cholesterol is known to be the precursor for vitamin D synthesis, and cholesterol removal is...