Fatih Temiz

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. Conflict of interest:None declared.

A homozygous recurring mutation in WISP3 causing progressive pseudorheumatoid arthropathy.

Abstract WISP3 is a member of the CCN (for CTGF, CYR61, and NOV) gene family, which encodes cysteine-rich secreted proteins with roles in cell growth and differentiation. Mutations in the WISP3 gene are associated with the autosomal recessive skeletal disorder, also known as progressive pseudorheumatoid arthropathy of childhood (PPAC). We diagnosed three siblings from a non-consanguineous family with PPAC. The patients were asymptomatic in early childhood. Signs and symptoms of disease that include progressive joint stiffness, swelling of the finger joints, and osteopenia, and slow linear growth developed between 2 and 8 years of age. PCR amplification and direct sequencing of the WISP3 gene revealed a homozygous mutation at nucleotide 156 of the WISP3 gene, resulting in a Cys52-to-ter substitution. This mutation has previously been reported in French, Italian, and Arab families. Interestingly, the C52X mutation was found to be associated with a c.248G→A (G83E) variation, suggesting the existence of a founder effect. By contrast, the presence of the same aberration in three different ethnic groups could imply that this particular site is prone to mutation. Basal fasting concentrations of growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3, as well as glucose and insulin levels revealed no aberrations. In conclusion, consideration of this rare disease that causes significant morbidity with short stature, osteopenia and arthritic complaints would prevent unnecessary examinations and treatment attempts. Testing for this specific mutation in suspected cases could provide a rapid and definitive diagnosis.

Chromium levels in healthy and newly diagnosed type 1 diabetic children

Background:  The aim of this study was to compare the chromium levels of plasma (PCL), erythrocyte (ECL) and urine (UCL) in type 1 diabetics and healthy subjects and to review the relation between metabolic parameters.

Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS1R gene in three unrelated families

The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, KISS1R mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism.

Novel growth hormone receptor gene mutation in a patient with Laron syndrome.

ABSTRACT Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation.

Ecthyma gangrenosum in a previously healthy pediatric patient and associated facial paralysis and persistent hyperplastic primary vitreous.

Summary Background: Ecthyma gangrenosum is an infective lesion of the skin and mucosal membranes. It is most commonly caused by Pseudomonas aeruginosa, and the most important risk factors are malignancy and neutropenia. However, it has rarely been reported in children who were previously healthy. Persistent hyperplastic primary vitreous has been described as the persistence of the fetal hyaloid vascular system. Acute otitis media with facial paralysis is an infrequent association. Case Report: We report the case of a 5-month-old boy hospitalized because of fever, otorrhea and necrosis on his body. He had peripheral facial paralysis on the same side as otorrhea. Leukocoria was determined in the right eye. He had many gangrenous ulcers on the extremities and body. Conclusions: We present a previously healthy pediatric patient diagnosed with persistent hyperplastic primary vitreous, ecthyma gangrenosum (by the septicemia of P. aeruginosa), and peripheric facial paralysis (a complication of acute otitis media), admitted to hospital.

Low Serum Adiponectin Levels in Children and Adolescents with Diabetic Retinopathy

OBJECTIVE The aim of this study was to elucidate the role of adiponectin, leptin, TNF-α and IL-6 on the early detection of the microvascular complications of type I diabetes. MATERIALS AND METHODS A total of 88 children were included in the study. There were 60 type I diabetic patients and 28 healthy control children. RESULTS The gender, age, weight, height, BMI and puberty status characteristics were similar in the patient and control groups (p>0.05). The serum leptin, TNF-α and IL-6 levels were similar between the patient and control groups (p>0.05) and the only difference was in the serum adiponectin level which was higher in the patient group (p:0.042). We also found no association between the adiponectin, leptin, TNF-α and IL-6 levels and diabetes duration (p>0.05). Leptin was high in the pubertal period (p:0.016), while adiponectin TNF-α and IL-6 levels were similar in the prepubertal and pubertal periods (p>0.05). The serum leptin level was high in microalbuminuria patients (p<0.041). The serum adiponectin, TNF-α, and IL-6 levels were not different in patients with and without microalbuminuria (p>0.05). The serum adiponectin level was lower in diabetic retinopathy patients (p:0.003), while the serum leptin level was higher (p:0.003). The TNF-α and IL-6 levels were similar in patients with and without retinopathy (p>0.05). CONCLUSION We found increased serum adinopectin levels in children and adolescents with type I diabetes mellitus and low levels in diabetic retinopathy patients. Patients with low serum adiponectin levels and high leptin levels should be more closely monitored for chronic complication development and better metabolic control should be aimed for.

An Association of Leishmaniasis and Dyserythropoiesis in Children

Visceral leishmaniasis results in hematological problems such as cytopenias and coagulopathies. This disorder also has morphological effects on the bone marrow. Dyserythropoiesis is one of the most prominent seen with changes like multilobed nuclear cells and the appearance of bridges between nuclei and cytoplasms. Approximately half of the children with leishmaniasis showed dyserythropoietic findings in bone marrow aspirate slides. Because this in endemic regions, physicians of these countries must be alert to correctly diagnose disease and discriminate from other dyserythropoietic disorders.

Diagnosis of chromosomal abnormalities in a patient with thanatophoric dysplasia (TD) type I: The first report describing an important association between cytogenetic findings and TD

Summary Background: Thanatophoric dysplasia (TD) is the most lethal and most severe type of dysplasia. It has distinct features, the most important of which is short tubular bones and short ribs with platyspondyly, allowing a precise radiologic and prenatal ultrasonographic diagnosis. It has been reported to be caused by mutations in the FGFR3 gene, but exactly how cytogenetic abnormalities might lead to TD is unclear. Case Report: We report a case of TD with different prenatal sonographic features compatible with the classification of type I. In the result of cytogenetic examination, we found de novo CAs in 28% of cells analyzed from the affected infant; 75% of the abnormalities were numerical, and of those, 25% were structural aberrations; 21% of cells revealed predominantly numerical aberrations. Monosomy 18, 21 and 22 was observed in 4% of cells, monosomy 20 in 2%, and monosomy 7, 8, 14, 17 and 19 in 1%. Structural changes were observed in 7% of cells. Conclusions: It appears that these chromosomes may be preferentially involved in and important for TD development.

The Investigation of Plasma Glucagon-like Peptide-1 Levels in Newly Diagnosed Type 1 Diabetic Children.

Objective To reveal the possible role of glucagon-like peptide-1 (GLP-1) in newly diagnosed Type 1 diabetic children. Methods Twenty-five newly diagnosed children and 22 healthy children were included in the study. Results In oral glucose tolerance tests, no correlation was observed between C-peptide and GLP-1 levels at 0 and 30 minutes, and plasma GLP-1 levels in both groups at 0 and 30 minutes were not statistically different. Conclusion Consequently, fasting and postprandial GLP-1 levels in newly diagnosed Type 1 diabetic children are not different from healthy children. Glucagon-like peptide-1 levels in newly diagnosed Type 1 diabetic children suggest that plasma GLP-1 levels do not have any role in the pathogenesis of Type 1 diabetes mellitus.