A case report of a patient with neurodevelopmental disorder with impaired speech and hyperkinetic movements: A biallelic variant in the ZNF142 gene.

Biallelic pathogenic variations in the zinc finger protein 142 (ZNF142) gene are associated with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This disorder is characterized by developmental delay, intellectual disability, speech delay, and movement disorders such as dystonia, tremor, ataxia, and chorea. Here, we report a patient who exhibited common neurological features and rarely reported brain MRI findings. Exome sequencing identified a novel biallelic variant in ZNF142 (c.3528_3529delTG; p.C1176fs*5 (NM_001105537.4)). NEDISHM was first described by Khan et al. (2019) and has been reported in 39 patients to date. Furthermore, upon reviewing our in-house data covering 750 individuals, we identified three different pathogenic ZNF142 variants. It appears that the frequency of ZNF142 alleles is not as low as initially thought, suggesting that this gene should be included in new generation sequencing panels for similar clinical scenarios. Our goal is to compile and expand upon the clinical features observed in NEDISHM, providing novel insights and presenting a new variant to the literature. We also aim to demonstrate that ZNF142 pathogenic variants should be considered in neurodevelopmental diseases.

Exploring genetic variants in congenital monosaccharide-disaccharide metabolism: Carrier ratios and phenotypic insights.

OBJECTIVES: Adverse food reactions, often underestimated, encompass congenital monosaccharide-disaccharide metabolism disorders, yielding diverse outcomes such as abdominal pain, diarrhea, bleeding disorders, and even death. This study retrospectively scrutinized genetic variants linked to these disorders in a cohort subjected to whole-exome sequence analysis (WES), determining carrier frequencies and genotype-phenotype correlations. METHODS: Data from 484 patients, were retrospectively analyzed using a gene panel (ALDOB, FBP1, GALE, GALK1, GALM, GALT, LCT, SLC2A2, SLC5A1, SI) for congenital monosaccharide-disaccharide metabolism disorders. WES was performed on patients using the xGen Exome Research Panel v2 kit, utilizing Next Generation Sequence Analysis (NGS). The study encompassed pathogenic, likely pathogenic, and variant of uncertain significance (VUS) variants. RESULTS: Among 484 patients (244 female, 240 male), 17.35% carried 99 variants (67 distinct) in the analyzed genes. Pathogenic/likely pathogenic allele frequency stood at 0.013, while VUS allele frequency was 0.088. Notably, 44% (37/84) of patients harboring mutations manifested at least one relevant phenotype. Carriage frequencies ranged from 1:25 (SI gene) to 1:968 (GALE gene), with the estimated disease frequency spanning from 1:2500 to 1:3748000. CONCLUSIONS: Our study underscores clinical manifestations in heterozygous carriers of recessive genetic disorders, addressing gaps in carrier frequencies and phenotypic effects for congenital monosaccharide-disaccharide metabolism disorders. This knowledge can improve these conditions' diagnosis and management, potentially preventing adverse food reactions and their associated complications.

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature.

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (MIM#617333) is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability (ID), and dysmorphic facial features due to pathogenic variations in the Bromodomain- and PHD Finger-Containing Protein (BRPF1) (MIM#602410) gene. Herein, we report the first Turkish patients with IDDDFP. Additionally, the patients had hematopoietic disorders such as anemia and thrombocytopenia, which have not been previously described in IDDDFP patients. Genetic testing using Whole Exome Sequencing (WES) revealed a novel heterozygous c.1433G > A; p.W478* (NM_004634.3) pathogenic variant on exon 3 of the BRPF1 gene. The patients demonstrated classical features of IDDDFP such as intellectual disability, developmental delay, ptosis, micro and retrognathia, and dysmorphic facial features, in addition to the anemia and thrombocytopenia. Apart from the variant in BRPF1, no additional genomic changes were detected by WES and chromosomal microarray analysis (CMA). Hopefully, our novel report on the hematopoietic anomalies of our patients due to BRPF1 will expand upon the clinical spectrum of IDDDFP, encourage further studies about BRPF1-hematopoietic system relations, and affect the diagnostic and therapeutic schemes of hematopoietic system disorders.

Re-evaluation of Genetic Variants in Parkinson's Disease Using Targeted Panel and Next-Generation Sequencing.

Parkinson's disease (PD) is a complex disorder with a significant genetic component. Genetic variations associated with PD play a crucial role in the disease's inheritance and prognosis. Currently, 31 genes have been linked to PD in the OMIM database, and the number of genes and genetic variations identified is steadily increasing. To establish a robust correlation between phenotype and genotype, it is essential to compare research findings with existing literature. In this study, we aimed to identify genetic variants associated with PD using a targeted gene panel with next-generation sequencing (NGS) technology. Our objective was also to explore the idea of re-analyzing genetic variants of unknown significance (VUS). We screened 18 genes known to be related to PD using NGS in 43 patients who visited our outpatient clinic between 2018-2019. After 12-24 months, we re-evaluated the detected variants. We found 14 different heterozygous variants classified as pathogenic, likely pathogenic, or VUS in 14 individuals from nonconsanguineous families. We re-evaluated 15 variants and found changes in their interpretation. Targeted gene panel analysis with NGS can help identify genetic variants associated with PD with confidence. Re-analyzing certain variants at specific time intervals can be especially beneficial in selected situations. Our study aims to expand the clinical and genetic understanding of PD and emphasizes the importance of re-analysis.

The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.

Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

Melatonin receptor gene polymorphisms as a risk factor in patients with diabetic peripheral neuropathy.

AIMS: Oxidative stress plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). Melatonin is one of the most powerful endogenous antioxidants and has anti-inflammatory properties. We investigated how the gene polymorphism of melatonin differs in patients with DPN compared to an healthy control group. MATERIALS AND METHODS: A total of 54 diabetic peripheral neuropathy patients who applied to the Neurology outpatient clinic between 2020 and 2021, and 53 healthy controls comparable with the patient group in terms of age and gender were included in the study. Electromyography was performed and the melatonin gene polymorphism was analysed using the pyrosequencing method. RESULTS: Melatonin gene variants rs2119882, rs13140012, and rs10830963 were analysed in patients and controls. The rs2119882 (G allele) has a protective role, and rs13140012 polymorphism has a related 5-fold higher risk of DPN in the recessive model. CONCLUSIONS: Melatonin gene polymorphisms have been shown to be associated with DPN. This is the first and only study investigating the relationship between melatonin gene polymorphisms and DPN. Ethnicity is very important in genetic studies, and it will give us more information on the role of melatonin gene variants in larger study groups of diabetic patients of other ethnic origin.

A new entity in the NARS2 variant: the first reported case of type 1 diabetes mellitus associated with the phenotype.

NARS2 mutations are known to cause various clinical phenotypes such as nonsyndromic hearing loss, Leigh/Alpers syndrome, refractory epilepsy, developmental delay, intellectual disability and myopathy. We presented the first Turkish variant of NASR2 and added type 1 diabetes mellitus (DM), which was not previously described in the phenotype spectrum of this disease. A 4.5-month-old girl presented with hearing loss, hypotonia, refractory myoclonic epilepsy, severe developmental delay and large subdural hemorrhage. In the first year of the follow-up, type 1 DM developed. A homozygous missense mutation, [c.500 A>G, p.H167R] in the NARS2 gene was detected in the trio-based whole-exome sequencing (WES). In this disease, in addition to multi-organ involvement, type 1 DM may also develop, as in our case. Since it is a mitochondrial disease, the decision to treat with valproic acid should be reconsidered. The long diagnostic process can be shortened with WES.

A New Mutation, Hb A2-Canakkale [δ10(A7)Ala→Val; HBD: c.32C>T], and Other Well-Known δ Variants Identified in a Selected Cohort with Low Hb A2 Levels.

Hemoglobinopathies are the most common single-gene disorders, and ß-thalassemia (ß-thal) imposes a tremendous health burden on Turkey. Thus, premarital carrier screening is obligatory in Turkey, as it is in some other countries. As a result of this mandatory procedure, at routine clinical checkups, many individuals who had undergone premarital screening but did not have any clinical symptoms and/or hematological findings, have compulsorily been required to undergo further evaluation due to abnormal levels of hemoglobin (Hb) fractions (Hb A, Hb A2 and Hb F). Many consequences, such as mutations in unrelated gene(s) or someone's nutritional status, have been reported to affect the Hb fractions levels. In the present study, we aimed to determine whether HBD has a molecular causative role in patients with low Hb A2 levels (below 1.8%). The study was conducted with 20 individuals with low Hb A2 levels who had applied to our outpatient clinic. All DNA samples were analyzed for the HBD gene. Nineteen of the 20 subjects were diagnosed to carry a mutation with one of four different δ-globin variants. Three of them had been described previously [Hb A2-Yialousa (HBD: c.82G>T), Hb A2-Bornova (HBD: c.350G>C) and Hb A2-Yokoshima (HBD: c.77G>A)]. The novel [δ10(A7)Ala→Val, HBD: c.32C>T] mutation was defined as a new δ variant and reported to the HbVar database as Hb A2-Canakkale. In conclusion, the molecular characterization of Hb A2 low levels has been suggested to be significant for a definite diagnosis and counseling.

Diagnostic Utility of Array Comparative Genomic Hybridization in Children with Neurological Diseases.

INTRODUCTION: We evaluated the contribution of array comparative genomic hybridization (aCGH) to the final diagnosis in children with neurocognitive disturbances or dysmorphic findings, but lacked a specific diagnosis. MATERIALS AND METHODS: Medical files of pediatric patients with neurocognitive disturbances who underwent aCGH analysis were reviewed retrospectively. RESULTS: Of 155 patients, 77 copy number variations were detected and 50% (39/77) were considered causative. The aCGH's final diagnostic rate was 25.1% (39/155). CONCLUSION: With aCGH analysis, the diagnosis rate for patients with undiagnosed neurocognitive disturbances or dysmorphic syndrome may increase by 25-30%. If the phenotypic findings of the widely known neurocognitive disturbances cannot be identified during the initial clinical assessment, aCGH analysis may be beneficial.

Copy number variations in patients with idiopathic recurrent pregnancy loss: an arrayCGH approach.

BACKGROUND: It is not always possible to determine the causative basis of pregnancy losses and even today it has been reported that 50% of cases with recurrent pregnancy loss (RPL) have no reason to be detected. In our study, it is aimed to reveal the copy number variations (CNVs) of the genes which presumably have a potential effect in individuals with RPL and contribute to subsequent functional studies in the follow-up. METHODS: We retrospectively evaluated the array-comparative genomic hybridization (aCGH) data of cytogenetically 64 normal individuals (21 couples, 11 unrelated women, and 11 unrelated men) who had applied to our outpatient clinic from January 2016 to December 2017, for the history of idiopathic two or more RPL. RESULTS: A total of 83 CNVs were detected in 56 different chromosomal regions [36% (20/56) is deletion and 64% (36/56) is duplication] in 40/64 (62.5%) of the cases. Two detected deleterious CNVs encompassing 1p36.22-p36.21 and 10q11.22 chromosomal locus have been reported as pathogenic according to the Database of Genomic Variants (DGV). DISCUSSION: CNVs that may play a role in the genetic etiology of idiopathic RPL were revealed in our study and potential chromosomal loci were introduced to the literature for further analysis. The detection of CNVs and their association with reproduction such as RPL, infertility, and even other diseases will allow us to have more information about the clinical consequences and will make it possible to provide more accurate and comprehensive genetic counseling.

MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss.

While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.

The prevelance of human papillomavirus (HPV) genotypes detected by PCR in women with normal and abnormal cervico-vaginal cytology.

OBJECTIVES: Cervical cancer is the second most common type of cancer for women worldwide with a great proportion proved to be related to human papillomavirus (HPV) infection. As infection with HPV is the strongest risk factor for cervical neoplasia, detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology seems to be of paramount importance in cervical cancer screening. The objective of the study is to evaluate the prevalence and HPV genotypes among women with normal or abnormal Pap smear tests. MATERIAL AND METHODS: This retrospective study was conducted in a tertiary care university hospital in western Turkey. A total of 201 patients in whom both HPV typing and Pap test was performed between 2012 and 2016 in our obstetrics and gynecology department were enrolled in this study. Clinical and laboratory data were obtained for all participants. Cervical smears of the patients were classified by the Bethesda system and HPV analyses were done using the polymerase chain reaction (PCR) method. RESULTS: This study included 201 women, 72 of whom had normal and 129 of whom had abnormal Pap smear results. HPV DNA was detected in 91 (45.2%) of the 201 investigated women. Out of 72 patients with normal cervico-vaginal cytology, HPV positivity was detected in 35 (49%) patients, whereas 33 (35%) patients out of 94 with ASCUS , 18 (62%) patients out of 29 with LSIL and 5 (83%) patients out of 6 with HSIL had HPV positivity. Out of 35 HPV positive women that had normal pap test results, 25 (75%) were found to have high risk HPV (HR-HPV) genotypes. In women with ASCUS, LSIL and HSIL, HR-HPV genotype rates were found to be 94%, 89% and 100% respectively. The most common identified HPV types were HPV58, HPV16, HPV31, HPV33, HPV11 and HPV35. CONCLUSIONS: The frequency of HPV infection was found to be higher in our study compared to previous reports. Moreover, although HR-HPV genotypes were also detected in patients with normal cervical cytology, a majority of patients with HR-HPV genotypes were associated with abnormal cervical smear cytology including high rates of atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion.

Is there any increased risk of hypertension, diabetes and cardiac diseases in psoriatic patients with TNF-α G238A and G308A polymorphism?

INTRODUCTION: Psoriasis is regarded as a complex autoimmune disease with strong genetic background. Psoriatic patients suffer from many comorbidities including hypertension, diabetes and cardiovascular diseases. Cytokines such as tumor necrosis factor α (TNF-α) may be a key player that triggers psoriasis and diabetes, hypertension and cardiac disease at the same time. AIM: To evaluate genetic variations in the TNF-α region and its association with psoriasis and related comorbidities. MATERIAL AND METHODS: The study covered 129 psoriasis patients with three main subgroups with coronary artery disease (n = 41), hypertension (n = 35), and diabetes (n = 21). DNA samples were genotyped for TNF-α G308A and G238A polymorphisms by real-time polymerase chain reaction melting-curve analysis and results were compared statistically. RESULTS: Psoriatic patients with both TNF-α-298 and TNF-α-308 polymorphisms showed no statistically significant increase in the risk of hypertension (OR = 0.425, χ² = 1.76, p = 0.18 and OR = 1.87, χ² = 1.33, p = 0.25), coronary artery disease (OR = 1.97, χ² = 1.91, p = 0.17 and OR = 2.63, χ² = 1.35, p = 0.25), or diabetes (OR = 1.35, χ² = 0.24, p = 0.62 and OR = 1.53, χ² = 0.24, p = 0.62). CONCLUSIONS: The current preliminary results suggested that there was no correlation between TNF-α promoter polymorphism and diabetes, hypertension and cardiac disease among psoriatic patients in the Turkish population.

The relationship between obstructive sleep apnea syndrome and apolipoprotein E genetic variants.

BACKGROUND: Clinical and epidemiological studies indicate that obstructive sleep apnea syndrome (OSAS) has a strong genetic basis. OBJECTIVES: To investigate the apolipoprotein E (APOE) alleles as a genetic risk factor in OSAS. METHODS: A total of 73 patients (37 male) were included. All underwent full-night polysomnography and were evaluated for APOE alleles. RESULTS: The mean age was 51 ± 12 years. Forty-two of the patients had OSAS. The APOE3 allele was found in 97.3% (71/73) of the study population. The most common APOE genotype was E3/E3 (55/73, 75.3%). Compared to the individuals with no APOE2 alleles (E3/E3, E3/E4), the individuals with at least one APOE2 allele (E2/E3, E2/E4) had a 9.37-fold greater OSAS risk (OR = 9.37, 95% CI 1.13-77.7, p = 0.019). The individuals with APOE2 alleles (E2/E3, E2/E4) compared to the individuals with only an E3/E3 allele genotype had a 10-fold greater OSAS risk (OR = 10.3, 95% CI 1.24-86.61, p = 0.0308). Compared to the individuals with no APOE4 alleles (E2/E3, E3/E3), the individuals with APOE4 alleles (E2/E4, E3/E4) had a high but insignificant risk for OSAS (OR = 2.9, 95% CI 0.55-15.05, p = 0.286). The individuals with APOE4 alleles (E2/E4, E3/E4) compared to APOE3 alleles (E3/E3) had an increased but insignificant risk for OSAS (OR = 3.62, 95% CI 0.96-19.05, p = 0.127). CONCLUSION: Specific APOE genotypes are associated with OSAS in a high-risk population.

Bcii--RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in chronic renal failure patients requiring long-term hemodialysis.

BACKGROUND AND AIM: There is an increased mortality risk in long-term hemodialysis patients of renal failure due to the chronic inflammation. The relationship between the chronic renal failure (CRF) and the role of familial genetic markers remains incompletely understood. In the current study, it was aimed to find out the prevalence of common MEFV gene mutations and BcII polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who require long-term hemodialysis. METHOD: Current cohort includes 242 CRF patients and 245 healthy individuals from the same population. Total genomic DNA was isolated from peripheral blood-EDTA samples and genotyping of target MEFV gene was carried out by reverse hybridization Strip Assay and real-time techniques. The SAA1 gene was genotyped by the BclI-RFLP method. RESULTS: Increased mutated MEFV genotypes were found in current CRF patients when compared with the control group from the same ethnicity and the difference was statistically significant (Table 2) (OR: 4.9401, 95% CI: 3.0694-7.9509), p<0.0001. The most frequent point mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene was also different when compared with the healthy controls and the difference was found to be statistically significant (χ2: 13.18; p=0.000). CONCLUSIONS: The current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.

Contribution of the STAT4 rs7574865 gene polymorphism to the susceptibility to autoimmune thyroiditis in healthy Turk population and psoriatic subgroups.

INTRODUCTION: STAT4 is an important transcription factor that activates gene transcription as a response to cytokines. Recently, the influence of STAT4 gene on autoimmune disease has been widely studied in many different immune-related diseases. Autoimmune, metabolic and cardiovascular disorders are more common in psoriatic patients. STAT4 may be a unique gene that switches on in autoimmune-related thyroid disease in psoriatic patients. THE AIM OF THE STUDY: To explore the association of a STAT4 rs7574865 polymorphism to autoimmune thyroid diseases in the general Turkish population and psoriatic subgroups. MATERIAL AND METHODS: A total of 132 psoriatic patients and 118 non-psoriatic volunteers were genotyped for STAT4 rs7574865 using real time PCR. Twenty-four of the psoriatic patients and 15 of the non-psoriatic volunteers have autoimmune-related thyroid diseases. RESULTS: The prevalence of the T allele [OR = 4.37; 95% CI: 1.05-19; p = 0.03] of the STAT4 rs7574865 was higher in individuals with autoimmune-related thyroid diseases among the all non-psoriatic volunteers. The volunteers with autoimmune-related thyroid diseases has an increased allele positivity and carriers having at least one of the risk allele was significantly higher than in counterparts with a GG wild genotype [ORGT/TT vs. GG: 1.73; 95% CI: 0.09-32; p = 0.03]. Yet, there was no evidence of an association between rs7574865 and autoimmune-related thyroid disease in psoriatic patients. CONCLUSIONS: The STAT4 rs7574865 polymorphism increases autoimmune-related thyroid disease susceptibility among the general population but not in psoriatic patients.

Intercellular adhesion molecule-1 K469E and angiotensinogen T207M polymorphisms in coronary slow flow.

OBJECTIVE: To investigate intercellular adhesion molecule-1 (ICAM1) and angiotensinogen (AGT) gene polymorphisms, as related to atherosclerosis and endothelial dysfunction, in coronary slow flow (CSF). SUBJECTS AND METHODS: The participants in this study were 48 patients with CSF and 67 patients with normal coronary flow as controls. The K469E polymorphism of ICAM1 (rs5498) and the T207M polymorphism of AGT (rs4762) were determined using the polymerase chain reaction amplification method. RESULTS: Baseline demographic parameters were similar in both groups. The mean thrombolysis in myocardial infarction frame count was significantly higher in patients with CSF (23.8 ± 5.1) compared to the controls (13.3 ± 2.6, p < 0.001). A significant association was found between the ICAM1 K allele and CSF (OR: 1.96, 95% CI: 1.15-3.35, p = 0.013). There was no difference in the frequency of AGT T207M genotypes in the patients with CSF and the control subjects. CONCLUSION: This study showed that K469E polymorphisms of ICAM1 that play a role in atherosclerotic pathogenesis are related to CSF.

Evaluation of Smooth Muscle Myosin Heavy Chain Isoform Expressions in a Buried Penis.

BACKGROUND: A buried penis (BP) is rare in which the penile body is retracted into the prepubic adipose tissue. This research focuses on differences in smooth muscle myosin heavy chain (SMMHC) isoform expressions in the dartos fascia. METHODS: A total of 82 children, 41 of whom had BPs, who applied for circumcision between May and November 2021, were included in the study. The cases were divided into four groups aged ≥6 years (NP6, n = 18) and aged ≤3 years (NP3, n = 17) with normal penile appearance, aged ≥6 years (BP6, n = 23) and aged ≤3 years (BP,n = 24) with a BP. SMMHC isoforms mRNA gene expression analyses were performed by quantitative PCR technique in dartos fascia obtained from foreskin removed by circumcision. RESULTS: Compared to the NP3 group, the SM1 mRNA expressed in the BP6 group was statistically significantly higher (p < 0.005). SM2 mRNA levels expressed in dartos fascia were considerably higher in NP6 and NP3 groups compared to BP6 and BP3 groups (p < 0.001). The SM2/SM1 ratio was 0.85 in the BP6 group and 1.46 in the NP6 group, which was statistically significant (p = 0.006) and increased from 0.87 in the BP3 group to 2.21 in the NP3 group (p < 0.001). CONCLUSION: In a buried penis, there is a difference in the expression of SMMHC isoforms. SM1 is highly expressed, while SM2 decreases, increasing the SM2/SM1 ratio. This causes increased contractility in the smooth muscle, leading to retraction of the penile body. The dartos fascia surrounding it resembles aberrant muscle tissue in boys with a BP. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Case-control study.

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene.

Introduction: Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele. Methods: A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups. Results: Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035). Conclusion: Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas.

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.