Copy Number Variations Analysis Identifies QPRT as a Candidate Gene Associated With Susceptibility for Solitary Functioning Kidney

BackgroundThe lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.MethodsIn our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.ResultsBesides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.ConclusionOur data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.

Zonisamide as treatment option in persistent migraine aura

Persistent migraine aura without infarction is a rare but debilitating condition. Treatment options are mostly anecdotal and limited due to inefficacy and side effects. We present a 16-year-old female patient with triple X syndrome, having persistent aura symptoms for over 2 years, consisting of continuous visual and sensory sensations. Previous treatments with seven different migraine preventatives were not successful. The patient successfully responded to zonisamide against refractory prolonged aura and remained symptom-free under the ongoing treatment without any relevant side effects. Zonisamide may be considered a new and safe treatment option for patients with persistent migraine aura.

Chromosomal abnormalities predisposing to infertility, testing, and management: a narrative review

Background Much interest has not been placed on the role of chromosomal abnormalities in the pathogenesis and rising prevalence of infertility in recent times. This review was conducted to renew public interest on the chromosomal basis of infertility, testing, and management. Main text Meiotic and post-zygotic mitotic errors may cause infertility-predisposing chromosomal abnormalities, including Klinefelter syndrome, Jacob syndrome, Triple X syndrome, Turner syndrome, and Down syndrome. Chromosomal abnormalities such as deletion, translocation, duplication, inversion, and ring chromosome may also predispose to infertility. Notable features of male chromosomal infertility include spermatogenic failure, characterized by azoospermia, oligospermia, and gonadal dysgenesis, while females include premature ovarian insufficiency, amenorrhea, spontaneous abortion, and gonadal dysgenesis. The risk of these abnormalities is influenced by maternal age and environmental factors such as chemical exposure, smoking, and alcohol consumption. Most chromosomal abnormalities occur spontaneously and are not treatable. However, early prenatal screening and diagnostic tests can lessen the effects of the conditions. There is also a growing belief that certain diets and drugs capable of changing gene expressions can be formulated to neutralize the effects of chromosomal abnormalities. Conclusion Meiotic and mitotic errors during gametogenesis and fetal development, respectively, can cause chromosomal abnormalities, which predispose to infertility. Couples who are at increased risk, particularly those with a family history of infertility and women at an advanced age (≥ 35 years), should seek medical advice before getting pregnant.

Social functioning and emotion recognition in adults with triple X syndrome

Background Triple X syndrome (TXS) is caused by aneuploidy of the X chromosome and is associated with impaired social functioning in children; however, its effect on social functioning and emotion recognition in adults is poorly understood. Aims The aim of this study was to investigate social functioning and emotion recognition in adults with TXS. Method This cross-sectional cohort study was designed to compare social functioning and emotion recognition between adults with TXS (n = 34) and an age-matched control group (n = 31). Social functioning was assessed with the Adult Behavior Checklist and Social Responsiveness Scale for Adults. Emotion recognition was assessed with the Emotion Recognition Task in the Cambridge Neuropsychological Test Automated Battery. Differences were analysed by Mann-Whitney U-test. Results Compared with controls, women with TXS scored higher on the Adult Behavior Checklist, including the Withdrawn scale (P < 0.001, effect size 0.4) and Thought Problems scale (P < 0.001, effect size 0.4); and higher on the Social Responsiveness Scale for Adults, indicating impaired social functioning (P < 0.001, effect size 0.5). In addition, women with TXS performed worse on the Emotion Recognition Task, particularly with respect to recognising sadness (P < 0.005, effect size 0.4), fear (P < 0.01, effect size 0.4) and disgust (P < 0.02, effect size 0.3). Conclusions Our findings indicate that adults with TXS have a higher prevalence of impaired social functioning and emotion recognition. These results highlight the relevance of sex chromosome aneuploidy as a potential model for studying disorders characterised by social impairments such as autism spectrum disorder, particularly among women.