A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature

Objectives: The present study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study based on history, physical examination, typical radiological features, molecular and histo - pathological laboratory tests and a review of the literature. Study Design: This study began with a 7-year-old boy who was referred due to mandibular overgrowth. A pan - oramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws suggestive of cherubism. Overall, a total of four family members were tested for SH3BP2 mutations, namely two siblings and their parents. Both siblings had been clinically diagnosed with cherubism; however, the parents were clinically normal. Periph - eral blood was collected from all participants and genomic DNA sequencing was carried out. Results: A missense mutation was found in the two affected siblings and their asymptomatic mother. The mu - tation was a 1244 G>A transversion which resulted in an amino acid substitution from arginine to glutamine (p.Arg415Gln) in exon 9. Conclusions: The present study emphasized the importance of further clinical and molecular investigation even when only a single case of cherubism is identified within a family. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important insights into the molecular mechanisms associated with this disease

Detection of Novel NF1 Variants with Next-Generation DNA Sequencing Technology and Genotype-Phenotype Characteristics of Neurofibromatosis

MakaleWOS:000925992500001Objective: Neurofibromatosis type 1 (NF1, #162200) is a common neurological disorder with de novo or inherited germline mutations of the Neurofibromin (NF1, *613113). The purpose of this study is to increase the limited knowledge of NF1 in a small population-based dataset. Materials and Methods: This study enrolled patients with clinically suspected NF1 referred to the Kayseri Training and Research Hospital, Medical Genetics Department, between 2015 and 2017. The local ethics committee approved this study. Next-generation sequencing was performed for the genetic analysis. The genetic, demographic, and clinical features of the participants were characterized. Results: A total of 79 cases of NF1 were included. Of these cases, 40 were male, and 39 were female. The mean age was 11.9 years, and most were younger than 18 years. The most common complaint was cafe au lait macules. The 61 (77.3%) patients had pathogenic variants, and 16 (26.2%) were novel. Mostly affected mutation sites were exonic regions (n=54, 88.5%). The most common mutated exon was exon 38 (n=7, 11.5%), and most of the detected mutations were nonsense mutations (31%). Conclusion: It is one of Turkiye's largest NF1 study groups, where all exons of the NF1 gene were analyzed. This study contributes novel variants to the literature. There was no mutational hotspot region, and no significant relationship between genotype and phenotype was observed. Further studies and large sample sizes are required to better understand the relationship between NF and genetic changes

THE ROLE OF CHROMOSOME ANALYSIS IN MALEAND FEMALE INFERTILITY

Objective: Infertility is defined as absence of a healthy baby or pregnancy despite a one-year regular unprotected sexual intercourse. While primary infertility is called the absence of pregnancy at all, secondary infertility is called inability of couples who have had at least one healthy child to become pregnant. Chromosome anomalies are an important cause of both male and female infertility. In this study, we aimed to discuss the results of chromosome analysis of couples with primary infertility.Material and Methods: A total of 535 people, 262 women and 273 spouses with primary infertility, were included in the study. Chromosome analysis was performed using standard cytogenetic GTG banding technique using peripheral blood lymphocytes.Results: Normal chromosome establishment was detected in 513 people, 46,XX in 254 people, 46,XY in 259 people (95.8%). Eight patients had a normal chromosome variant (1.4%). In addition, translocation was detected in 5 patients (0.8%); in 4 patients, balanced reciprocal translocation and in 1 patient, Robertsonian translocation. Klinefelter syndrome was detected in 3 patients (1% of male infertility). In addition, we detected Turner syndrome variants, mos 45,X[11]/46,XX,i (X)(q10)[29] and mos 45,X[10]/46,X,i(X)(q10)[10] (0.7% of female infertility) in two cases. If normal chromosome variants are excluded, the frequency of the remaining changes in the patient population is 2.6%.Conclusion: Structural chromosomal anomalies such as balanced reciprocal and Robertsonian translocations cause both female and male infertility. 47,XXY should be kept in mind for male infertility and 45,X/46,X,i(X)(q10) Turner chromosome variants should be kept in mind in female infertility. In summary, chromosome analysis is one of the important tests that should be done to explain the etiology of both male and female infertility

A Frequent Mutation in the FTL Gene Causing Hyperferritinemia Cataract Syndrome in Turkish Population Is c.-160A>G

Objective: Hyperferritinemia cataract syndrome (HFCS) is an autosomal dominantly inherited disease characterized by increased serum ferritin levels and bilateral cataract formation in the early period of life. Heterozygote mutations in the 5’ untranslated region of the L-ferritin gene (FTL) have been reported to cause this disease. In this study, our purpose was to research the FTL gene mutations that cause HFCS in Central Anatolia and the clinical effects of these mutations. Materials and Methods: Seventeen patients from 6 families with high ferritin levels in performed serum measurements, those who were found to have cataracts in eye examinations, and families with vertical inheritance, since the disease is autosomal dominant, were included in the study. Exons, exon-intron boundaries, and 5’ and 3’ untranslated regions of FTL (NM_000146) were sequenced using the Sanger sequencing method. Results: The female/male ratio of the patients was 7/10. All of the patients were found to have c.-160A>G heterozygous mutation in the FTL gene. Conclusion: In the Turkish population, the prevalence of HFCS is about 1/100,000 and the commonly observed mutation is c.-160A>G mutation

A Case of Dichorionic Twin Pregnancy Concordant for Bilateral Cleft Lip and Palate and Discordant for Spina Bifida; Schisis Association

Backround: The schisis theory suggests that neural tube defect (NTD), cleft lip and palate (CL/P), omphalocele and diaphragmatic hernia are associated to each other more frequently than at the expected random combination rates in a given fetus. However, it is unusual to see schisis-associated defects concordantly in dichorionic twin pregnancy with other schisis-associated and non-associated defects. In addition, the association of lower limb oligodactly with oral cleft and spina bifida has not been reported before. Case: A 24-year-old woman with twin gestation at 21 weeks was referred to our unit. At ultrasound examination, bilateral CL/P and single umbilical artery in male fetus, and bilateral CL/P and open lumbar spina bifida in female fetus were revealed. At autopsy, oligodactyly of both lower limbs was demonstrated in the female fetus. The parents had no family history of NTD and CL/P. There was no consanguinity, nor was the mother exposed to teratogens

AN UNCOMMON CAUSE OF INFERTILITY: Y;1 TRANSLOCATION AND PGD TRIAL

WOS: 000343073900016PubMed ID: 25365861