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.     

Syrian refugee children face more peer victimization in schools what leads to poor mental health: a brief report

European Child & Adolescent Psychiatry -     

Prepubertal Unilateral Gynecomastia: Report of 2 Cases

Prepubertal unilateral gynecomastia is an extremely rare condition. At present, its etiology and management strategy are not well known. Two unrelated prepubertal boys of ages 8 and 9 who presented with complaints of unilateral enlargement of breast tissue are reported. Physical examination, biochemical, hormonal and oncologic work-up findings were normal. Both patients were treated with peripheral liposuction successfully. Histopathological and immunohistochemical examinations showed benign fibroglandular gynecomastia and intensive (3+) estrogen receptor expression in 100% of periductal epithelial cells. Although an extremely rare and generally benign condition, patients with prepubertal unilateral gynecomastia should have a full endocrine and oncologic work-up.     

Assessment of peripapillary retinal nerve fiber layer thickness in children with vitamin B12 deficiency

Purpose

Vitamin B₁₂ deficiency is a worldwide problem. It affects all ages, including children. It is one of the most common nutritional disorders and can cause harmful effects on the nervous system. In this study, we compared the peripapillary retinal nerve fiber layer thickness (RNFLT) in a healthy control group with children with vitamin B₁₂ deficiency. In our study, we aimed to evaluate the effect of vitamin B₁₂ deficiency on the RNFLT in children with the optical coherence tomography (OCT) method.

Methods

Sixty-six children with a diagnosis of vitamin B₁₂ deficiency (patient group) and 66 age- and sex-matched healthy children (control group) were enrolled in this prospectively designed study. Blood counts, vitamin B₁₂ levels, folate levels, and full biochemical parameters were obtained for all the subjects in each group. Peripapillary RNFLT measurements were performed with Cirrus HD spectral domain OCT.

Results

The thickness of the superior retinal nerve fiber layer (RNFL) in the vitamin B₁₂ deficiency group was significantly lower than that of the control group (p?=?0.037). Although the average thickness of the RNFL was lower in the patient group, there was no statistically significant differences (p?=?0.216). In the vitamin B₁₂ deficiency group, the average RNFL thickness and the superior RNFL thickness were significantly correlated with vitamin B₁₂ levels (r ₁?=?0.353, p ₁?<?0.004 and r ₂?=?0.416, p ₂?=?0.001, respectively).

Conclusion

Our study showed that a deficiency in vitamin B₁₂, elsewhere it is important for the development of the central nervous system, is associated with a reduction in the thickness of the superior RNFL.     

Identification of Three Novel and One Known Mutation in the WFS1 Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.     

Distinguishability analysis of an induced current EIT system using discrete coils

The distinguishability of a discrete coil induced current electrical impedance tomography system is analysed. The solution methodology of the forward problem of this system is explained. An optimization procedure using this forward problem solution is developed to find optimum currents that maximize the distinguishability. For the concentric inhomogeneity problem, it is shown that the coil currents can be optimized to focus the current density in any desired location, in the field of view. Optimum coil currents under the constraints of limited peak coil currents and limited total power are determined. Examples that demonstrate the performance of the system are presented.     

When should we operate on major fractures in patients with severe head injuries?

BACKGROUND: The widely accepted practice of early fracture fixation (EFF) in multiply injured patients has recently been challenged in the presence of head injury. DATA SOURCES: English and German language articles on the subject were searched using Medline. Keywords included head trauma, intracranial trauma, brain injuries, fractures, fracture fixation, timing, femur fracture, and tibia fracture. CONCLUSIONS: The available literature does not provide clear-cut guidance on the management of fractures in the presence of head injuries. The trend is toward a better outcome if the fractures are fixed early. Treatment should therefore be tailored to the individual patient, with the assumption that full neurologic recovery will take place.     

Primary pleural lymphoma: an unusual presentation of childhood non-Hodgkin lymphoma

A case of primary pleural non-Hodgkin lymphoma in a 2.5-year-old girl is reported. The patient had pleural involvement as the initial and only manifestation of the disease. Histopathalogic examination showed lymphoblastic lymphoma of T-cell origin. The child received the modified LSA2-L2 protocol. During the maintenance treatment, she had an isolated central nervous system relapse and died of neutropenic sepsis. To the authors' knowledge this represents the first case report of primary pleural lymphoma in the childhood period.