Healthy Female Controls Research Articles

Can sex influence the neurocognition of language? Evidence from Parkinson's disease

Parkinson's disease (PD), which involves basal ganglia degeneration, affects language as well as motor function. However, which aspects of language are impaired in PD and under what circumstances remains unclear. We examined whether lexical and grammatical aspects of language are differentially affected in PD, and whether this dissociation is moderated by sex as well as the degree of basal ganglia degeneration. Our predictions were based on the declarative/procedural model of language. The model posits that grammatical composition, including in regular inflection, depends importantly on left basal ganglia procedural memory circuits, whereas irregular and other lexicalized forms are memorized in declarative memory. Since females tend to show declarative memory advantages as compared to males, the model further posits that females should tend to rely on this system for regulars, which can be stored as lexicalized chunks. We tested non-demented male and female PD patients and healthy control participants on the intensively studied paradigm of English regular and irregular past-tense production. Mixed-effects regression revealed PD deficits only at regular inflection, only in male patients. The degree of left basal ganglia degeneration, as reflected by right-side hypokinesia, predicted only regular inflection, and only in male patients. Left-side hypokinesia did not show this pattern. Past-tense frequency effects suggested that the female patients retrieved regular as well as irregular past-tense forms from declarative memory, whereas the males retrieved only irregulars. Sensitivity analyses showed that the pattern of findings was robust. The results, which are consistent with the declarative/procedural model, suggest a grammatical deficit in PD due to left basal ganglia degeneration, with a relative sparing of lexical retrieval. Female patients appear to compensate for this deficit by relying on chunks stored in declarative memory. More generally, the study elucidates the neurocognition of inflectional morphology and provides evidence that sex can influence how language is computed in the mind and brain.

Activation of the Innate Immune System in Children With Irritable Bowel Syndrome Evidenced by Increased Fecal Human β-Defensin-2

The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation. Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n= 116), FAP (n= 33), and healthy control (HC) children (n= 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care. β-defensin-2 concentration was greater in children with IBS (P= .003) and FAP (P= .03) than in HCs. β-defensin-2 was greater in girls with IBS than female HCs (P= .007) and in girls with IBS vs boys with IBS (P= .036). There was no difference by sex in the FAP and HC groups. For the entire cohort, β-defensin-2 correlated with multiple pain symptoms. In the IBS group, β-defensin-2 correlated with pain interference (P= .014). No correlation with pain was found in the FAP or HC group. Gut permeability was greater in the IBS vs the FAP and HC groups (P=.038). For the entire cohort, permeability correlated with the number of pain episodes (P= .041) and interfering pain episodes (P= .049). For the entire cohort there was a correlation between β-defensin-2 and permeability (P= .003), with borderline correlation in the IBS group (P= .086). For the cohort and IBS and HC groups, the number of bowel movements was modestly inversely related to fecal β-defensin-2 concentrations. Increased fecal β-defensin-2 concentration in children with IBS suggests activation of the innate immune system in some, which, along with increased gut permeability, appears related to abdominal pain symptoms. Sex is an important variable in interpreting β-defensin-2 concentration in children with IBS.

Expression Analysis of Long Non-coding RNA Lnc-DC in HLA-DRB1*15:01-Negative Patients with Multiple Sclerosis: A Probable Cause for Gender Differences in Multiple Sclerosis Susceptibility?

Multiple sclerosis is a disease that affects male and female patients differently. Several studies have been performed to explain the gender differences in MS susceptibility, but the genetic causes underlying gender differences remain unknown. The association between multiple sclerosis and the HLA-DRB1*15:01 haplotype has been confirmed to be female-specific. We hypothesized other immunological components such as lnc-DC may be gender-specific among multiple sclerosis patients, especially when MS patients are negative for the HLA-DRB1*15:01 allele. Therefore, the current study, considering the results of previous studies, aimed to evaluate the expression level of the lnc-DC gene in HLA-DRB1*15:01-negative female patients with relapsing remitting MS (RRMS). A total of 50 MS female patients and 50 female healthy controls were enrolled in this observational case-control study. HLA-DRB1*15:01, as a critical risk factor for MS, was ruled out in all patients. The peripheral blood mononuclear cells were obtained from all patients and total RNA was isolated and cDNA synthesis was carried out. The gene expression of lnc-DC was evaluated by real-time quantitative PCR. Our results have shown that lnc-DC expression level was significantly higher in total MS female patients compared with female controls (P = 0.0044). In addition, the correlation between lnc-DC with disease duration, EDSS, and age at onset did not reach a statistical significance in our study (r = 0.0336, P = 0.817; r = 0.0914, P = 0.5278 and r = 0.0743, P = 0.6083, respectively). Our results give further evidence that lnc-DC may play a gender-dependent role in MS pathogenesis.

Serum MyomiRs as Biomarkers for Female Carriers of Duchenne/Becker Muscular Dystrophy.

Background: Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked recessive lethal neuromuscular disease. MicroRNAs expressed in striated muscle, myomiRs, have been proposed as its potential biomarkers. Serum creatine kinase (CK) is commonly used as a biomarker in clinical practice, but it is not reliable. The aim of this study was to assess whether serum levels of myomiRs has diagnostic value for detection of female DMD/BMD carriers with normal or elevated CK.Methods: Thirty four female carriers and 33 age-matched healthy female controls were enrolled. Peripheral blood samples were collected and serum miRNAs were extracted for measurement of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 by quantitative real-time polymerase chain reaction.Results: MiR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 were upregulated in all female carriers in comparison to healthy controls. MiR-1 (Spearman's rho = +0.406, p = 0.017) was correlated with CK in the female carrier group. Receiver operating characteristic curve analysis of all seven myomiRs showed that the area under the curve (AUC) for miR-499, miR-133b, miR-1, miR-208b, and miR-133a exceeded 70.0%, and for miR-206 and miR-208a exceeded 60.0%. MiR-133b and miR-499 were significantly increased in all female carriers, even those with normal CK. AUC for the combination of all seven miRNAs was 87.2%. CK (OR 0.406, 95% CI 0.000–0.001, p < 0.0001) and miR-499 (OR 0.323, 95% CI 0.023–0.106, p = 0.003) were considered to be independent predictors for female carriers presence in the multivariable regression analysis model.Conclusions: MiR-133b and miR-499 are potentially useful biomarkers for female carriers with DMD/BMD (including those with normal CK). The combination of all seven serum miRNAs and their respective combinations with CK have better diagnostic value for female carriers than either CK or any separate miRNA.

Anti-Müllerian hormone concentrations in women with chronic kidney disease

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The effect of maternal protein restriction during perinatal life on the inflammatory response in pediatric rats.

Fetal growth restriction can affect health outcomes in postnatal life. This study tested the hypothesis that the response to an inflammatory pulmonary insult is altered in pediatric fetal growth restricted rats. Using a low-protein diet during gestation and postnatal life, growth-restricted male and female rats and healthy control rats were exposed to an inflammatory insult via the intratracheal instillation of heat-killed bacteria. After 6h, animal lungs were examined for lung inflammation and status of the surfactant system. The results showed that in response to an inflammatory insult, neutrophil infiltration was decreased in both male and female rats in the growth-restricted animals compared with the control rats. The amount of surfactant was increased in the growth-restricted animals compared with the control rats, regardless of the inflammatory insult. It is concluded that fetal growth restriction results in increased surfactant and altered neutrophil responses following pulmonary insult.

The influence of estrogen levels across the menstrual cycle on plantar loading and dynamic postural control in healthy females

The influence of estrogen levels across the menstrual cycle on plantar loading and dynamic postural control in healthy females

Pilot Study of Biomarkers of Oxidative Stress and Chlamydia trachomatis in Female Patients with Spontaneous Abortions

The aims of the present study were i. asses the biomarkers of oxi- dative stress including superoxide anion radical, Nitrite measurement and reduced glutathione in female patients with spontaneous abortions Asses the prevalence of C. trachomatis antibodies IgA and IgG in those patients, iii. Correlate the levels of the oxidative biomarkers to the presence of C. trachomatis antibodies. The study included one hundred female patients with 2 or more spon- taneous abortions in addition to one hundred healthy control females with normal gravidity and parity history. Blood samples were obtained from each subject and subjected to laboratory determination of super- oxide anion radical, Nitrite measurement and reduced glutathione by biochemical methods. Determination of specific immunoglobulin A and G (IgA, IgG) was determined by enzyme linked immunosorbent assay (ELISA). The prevalence of IgA and IgG for C. trachomatis in patients was 4% and 8% respectively and, in the control, subjects the prevalence of IgA and IgG were 1% and 2% respectively. The concentration of oxidative stress products was significantly higher in the patients group compared to the control group (P=0.0001). The concentrations of nitrite and reduced glutathione were 27.9± 4.7, 31.4± 1.9 nmol/ml respectively in patients and the concentrations of nitrite and reduced glutathione were 18.9± 2.1 and 27.9± 3.9 respectively in the control group. The concentration of SOD was significantly reduced in the patients group compared to the control group (P=0.0001). The concentration of SOD was 55.1 6.9 in the patients and in the control the concentration was 64.5± 7.7 nmol/ml In the study of oxidative stress markers in the patients with positive serology for C. trachomatis, there was significant increase in nitrite concentrations compared to patients negative for C. trachomatis sero- logical markers (P=0.005). While reduced glutathione concentration had insignificant increase in patients positive for C. trachomatis with reduced SOD compared to patients with negative serology to C. tra- chomatis, P=0.6, P=0.07, respectively. The present study highlights that there was significant increase in oxi- dant stress biomarkers nitrite and reduced glutathione with significant reduction in superoxide dismutase in patients with repeated abortions. The prevalence of IgG to C. trachomatis was significantly prevalent in patients with recurrent abortion compared to control subjects. The nitrite was significantly correlated with positive serology to C. tracho- matis.

Sex Hormones, BDNF, Leptin, and TGF-β1 in Females With IBS: A Pilot Investigation.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor βeta 1 (TGF-β1). Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-β1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed. Participants with IBS (n = 12) displayed higher estradiol (p = .027) than did HC (n = 21). Direction of associations among study variables often differed between groups: BDNF and progesterone in HC (rs = .623) and in IBS (rs = -.723). The relationship between log (CES-D) and log (estradiol) varied by IBS status (interaction term p = 0.019). Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-β1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

Altered pain modulation to noxious heat thermal stimuli in burning mouth syndrome.

The aim of this study was to examine temporal summation (TS) and conditioned pain modulation (CPM) in patients with burning mouth syndrome (BMS) and healthy controls using intra-epidermal electrical stimulation (IES). Twenty-six female patients with BMS and 27 healthy female controls participated in this study. A single stimulus with electrical stimulation followed by a train of 10 successive stimuli was administered to the right chin of participants in both the BMS and control groups. CPM was evaluated with the changes of TS calculated from the difference in numerical pain scale data between these two test stimuli and the following warm (40°C) and hot (47°C) conditioning stimuli applied at the non-dominant hand in both the BMS and control groups. TS was present in both the BMS and control groups. CPM in the BMS group was significantly less efficient at the 47°C condition than that in the control group, while no significant difference was observed in the CPM between the BMS and the control groups at the 40°C condition. These findings indicate that BMS is associated with a deficit inhibitory CPM and implicate the involvement of the central nervous system in the pathophysiology of BMS.

Evaluation of cognitive impairment in a French sample of patients with restrictive anorexia nervosa: two distinct profiles emerged with differences in impaired functions and psychopathological symptoms

PurposeThe cognitive profiles of patients suffering from anorexia nervosa (AN) are currently explored as potential facilitating and/or maintenance factors. Specific data in restrictive AN (AN-R) remain contradictory. This study focused on women with AN-R to evaluate their cognitive functions to develop a more specific cognitive remediation program.MethodsFemale patients older than 15 years who were suffering from AN-R were recruited in a specialized unit for eating disorder management. Female healthy control (HC) participants were recruited who were matched with AN patients on age. All participants completed a cognitive evaluation (premorbid intelligence quotient (IQ), planning, information processing speed, cognitive flexibility) and a clinical evaluation (impulsivity, anxiety, depression).ResultsA total of 122 participants were included. Patients suffering from AN-R had significant impairment in information processing speed and planning. Patients exhibited significantly better cognitive flexibility than did the HC group when adjustments were made for other cognitive functions and impulsivity. Two distinct subgroups of patients were identified. The first subgroup had more marked cognitive impairment and fewer psychopathological symptoms than did the second subgroup of patients and the HC group.ConclusionOur results highlight cognitive impairment in patients with AN who had normal premorbid IQ. Two distinct profiles emerge. In clinical practice, these results open up perspectives for the development of more specific cognitive remediation programs (one specific program for cold cognitions and another specific program targeting emotions and hot cognitions). These results warrant confirmation by larger studies with a more specific evaluation of the impact of emotional status.Trial registration NTC02381639, Date of registration. March 6, 2015

Differentially expressed lncRNAs in peripheral blood mononuclear cells from middle-aged female patients with rheumatoid arthritis-associated interstitial lung disease.

Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA) and has a large impact on the prognosis of RA, particularly among females, with an increased prevalence and severity compared with that of males. Here, we aimed to investigate the lncRNA profiles in peripheral blood mononuclear cells (PBMCs) from middle-aged female patients with RA-ILD to determine whether they could help diagnose RA-ILD. We collected PBMCs from middle-aged female healthy controls, and RA and RA-ILD patients, excluding those with known risk factors of RA-ILD, such as being elderly or male, smoking, and having a history of other diseases. Then, a microarray analysis was applied to profile the lncRNA and mRNA levels in 3 pairs of samples. qPCR was performed to evaluate the candidate lncRNAs from 20 participants of each group. The expression levels of NR_002819, NR_038935, and ENST00000603415 were significantly increased in the RA-ILD group, while the expression level of ENST00000560199 was significantly decreased. As risk factors for RA-ILD, the area under the curve (AUC) values of NR_002819, NR_038935, and ENST00000603415 were 0.858, 0.704 (medium diagnostic accuracy), and 0.976 (high diagnostic accuracy), respectively. As a protective factor for RA-ILD, the AUC of ENST00000560199 was 0.853(medium diagnostic accuracy). To the best of our knowledge, this is the first study of lncRNA profiles in RA-ILD. The expression levels of NR_002819 (MALAT1), NR_038935, ENST00000603415, and ENST00000560199 were significantly different in the RA-ILD group and could be potential biomarkers for the assessment and diagnosis of middle-aged female RA-ILD patients. Key Points • The expression profile of lncRNAs in PBMCs from RA-ILD patients was evaluated. • NR_002819, NR_038935, and ENST00000603415 increased in RA-ILD patients. •ENST00000560199 decreased in RA-ILD patients. • The 4 lncRNAs might be potential biomarkers for diagnosis of RA-ILD.

Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking

Background: Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. Objectives: We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). Methods: We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. Results: The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. Conclusions: Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.

Vitamin D receptor gene polymorphism in patients with osteomalacic myopathy in Egypt

Vitamin D works by binding to vitamin D receptor (VDR). The muscle involvement in hypovitaminosis D was broadly named osteomalacic myopathy. A case control study involved 20 female patients diagnosed with osteomalacic myopathy compared with 15 age-matched healthy female controls. We assessed both for VDR genotype single-nucleotide polymorphisms (SNP) at 3 sites (ApaI, BsmI, and FokI). ApaI and BsmI genotypes distribution in both groups showed non-significant difference unlike FokI genotypes in which we found significantly higher percentages of single allele mutation in patients vs. controls. The relation of VDR gene SNPs to muscle function was studied before but in healthy subjects. We tried to correlate if presence/absence of a certain mutation is responsible for the appearance of osteomalacic myopathy.

Treatment-Resistant Blunted HPA Activity, but Reversible Cardiovascular Stress Reactivity in Young Women With Eating Disorders

Previous research has provided evidence for a reduced neuroendocrine stress response in women with eating disorders (EDs). In the present study female in-patients with Anorexia and Bulimia nervosa were compared to female healthy controls (HC) before and after completing an in-patient treatment program. Salivary cortisol, alpha-amylase (sAA), heart rate response (HR), high-frequency heart rate variability (HF-HRV) and negative affective state were measured before, during and after exposure to the Trier Social Stress Test (TSST) at pre- and post-treatment. Patients with EDs (n = 13) showed significantly less ED symptoms at post-treatment. Compared to HC (n = 22), patients displayed a blunted cortisol stress response combined with overall attenuated sAA levels at pre-treatment. At post-treatment, the blunted cortisol stress response was still observable, while the differences in sAA responses disappeared. HR was attenuated at pre-treatment in patients, also indicated by a stronger HF-HRV throughout the TSST. These cardiovascular differences disappeared at post-treatment. Patients reported in general (pre- and post-treatment) more negative affect compared to HC. This study provides further evidences of a hypo-reactive hypothalamus–pituitary–adrenal axis (HPA) in patients with EDs which persists even after symptom recovery while initial low cardiovascular stress reactivity apparently can be restored by psychotherapy. Given the small sample size the findings have to be considered preliminary.

Variants and expression changes in PPAR-encoding genes display no significant association with schizophrenia.

A few studies suggested the contribution of PPARs to the etiology of schizophrenia (SCZ). However, it is still not clear whether variants in PPAR-encoding genes have a direct association with SCZ. The potential linkage between SCZ and the variants within PPAR encoding genes (PPARA, PPARD, and PPARG) was tested in a large cohort genome-wide association study (GWAS). Then, a mega-analysis was conducted using 14 gene expression profiling experiments in various human brain regions. Finally, the expression levels of the three PPAR-encoding genes were quantified in early-onset SCZ patients. Only one PPARG polymorphisms, rs62242085, presented a minor frequency deviation in the SCZ cohort (P-value = 0.035). None of the PPAR-encoding genes presented significant expression change within the brain regions profiled in 14 datasets acquired from different populations (P-value > 0.14) or in the whole blood of early-onset overall SCZ patients (P-value > 0.22). However, compared with healthy female controls, female early-onset SCZ patients presented a moderate but significant decrease in the expression level of PPARD (LFC = −0.55; P-value = 0.02) and a strong, but non-significant decrease in expression of PPARG (LFC = −1.30; P-value = 0.13). Our results do not support a significant association between variants in PPAR-encoding genes and SCZ, but suggest a necessity to explore the role of PPARD and PPARG in early SCZ phenotypes, specifically in females.

Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS.

Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI). Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA. ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly. Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8. ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.

Relationship Between Chronic Kidney Disease, Glucose Homeostasis, and Plasma Osteocalcin Carboxylation and Fragmentation

Chronic kidney disease (CKD) is associated with reduced insulin sensitivity, through mechanisms that are not well understood. Low vitamin K intake and incomplete carboxylation of the vitamin K-dependent protein osteocalcin may promote insulin resistance. We assessed relationships of osteocalcin concentration, carboxylation, and fragmentation with CKD and glucose homeostasis in a cross-sectional study. We included 87 participants without diabetes: 50 (27 female) with moderate to severe CKD (estimated glomerular filtration rate <60mL/min/1.73m2 not treated with dialysis) and 37 (17 female) healthy controls. Total osteocalcin was measured by immunoassay, and osteocalcin carboxylation and fragmentation status by liquid chromatography-electrospray ionization-based mass spectrometric immunoassay. Endpoints included glucose tolerance (based on 2-hour oral glucose tolerance test), insulin sensitivity (hyperinsulinemic-euglycemic clamp), and pancreatic beta-cell function (intravenous glucose tolerance test). The total plasma osteocalcin concentration was higher in the CKD group (mean [standard deviation] 102.9 [147.5]) than that in the control group (53.6 [51.1] ng/mL, P=.03), and more osteocalcin was circulating as fragments. The extent of osteocalcin carbocylation did not differ between individuals with and without CKD. Osteocalcin concentration, carboxylation, and fragmentation were not associated with any measure of glucose homeostasis in multivariable-adjusted analyses. In CKD, circulating osteocalcin concentrations are elevated, in part due to larger proportions of fragmented forms. However, osteocalcin carboxylation status is not significantly different between individuals with and without CKD. Our data also do not provide support for the hypothesis that differences in osteocalcin carboxylation may explain reduced insulin sensitivity in individuals with CKD.

Association between polymorphism in BMP15 and GDF9 genes and impairing female fecundity in diabetes type 2

BackgroundA shortened reproductive period and earlier menopause have been associated with type 2 diabetes. Growth differentiation factor 9(GDF9) and bone morphogenetic protein 15 (BMP15) gene mutations have been associated with earlier menopause. Therefore, this study aimed to evaluate the association between BMP15 and GDF9 mutations with impairing female fecundity in diabetic patients. The study subjects comprised 90 female diabetic patients and 60 female healthy controls. The physio-biochemical analysis was measured using enzymatic determination. A single-strand conformation polymorphism (SSCP) protocol was utilized to assess the pattern of genetic variations.ResultsGenotyping analysis of the BMP15 gene showed a heterogeneous pattern with the presence of two genotypes: AA and AC genotypes. Five novel missense single nucleotide polymorphisms (SNPs) were identified in the BMP15 gene: four SNPs detected in both genotypes, and Met4Leu, a specific SNP, was detected only in the AC genotype. Cumulative in silico tools indicated a highly deleterious effect for the Met4Leu on the mutant protein structure, function, and stability. Diabetes patients showed a significantly higher frequency of genotype AC. The physio-biochemical analysis of fasting plasma glucose (FBG), glycosylated hemoglobin (HbA1c), and luteinizing hormone (LH) were significantly higher (P < 0.05) in AC genotype than AA genotype.ConclusionsThe current research provides the first indication regarding the tight association of BMP15 polymorphism with the impairing female fecundity in the diabetic. A pivotal role is played by the novel (Met4Leu) SNP that can be used as a predictor for the impairing female fecundity of diabetes, while no polymorphism was found in exon 4 of the GDF9 gene.

Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy

BackgroundClassical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause autosomal dominant familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss.Case presentationHere, we report a patient with a lamin A specific pathogenic variant in exon 11, denoted LMNA (c.1745G > A; p.R582H), present in the homozygous state. Fat distribution was compared radiographically to an unrelated heterozygote LMNA p.R582H patient from another pedigree, a healthy female control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9), and typical FPLD2 (n = 8). The whole-body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, the p.R582H LMNA variant in homozygous fashion was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, the heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482.ConclusionsOur observations and radiological comparisons demonstrate an additive effect of LMNA pathogenic variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy.