Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.

Background: Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. Methods: A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. Results: The cohort comprised 172 pediatric patients, aged 0-5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. Discussion: Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.

Can platelet activation markers predict preeclampsia and/or its severity?

OBJECTIVE: This study aimed to evaluate the value of platelet activation markers in predicting preeclampsia and its severity. Preeclampsia is a serious pregnancy complication that affects 3-5% of pregnancies and can lead to significant morbidity and mortality for both the mother and the fetus. METHODS: The study included 99 patients diagnosed with preeclampsia and 60 healthy pregnant women as a control group. Platelet activation markers such as mean platelet volume (MPV), platelet distribution width (PDW), platelet count, and plateletcrit were evaluated along with other clinical parameters. RESULTS: The results of the study showed that platelet activation markers, particularly PDW and MPV, are valuable in the diagnosis and follow-up of preeclampsia. However, they are not sufficient to predict the severity of the disease. CONCLUSION: The study suggests that platelet activation markers could aid in predicting, diagnosing, and managing preeclampsia. However, further research is needed to determine the role of these markers in predicting the severity of the disease. The findings of this study could contribute to the development of more effective strategies for the prevention and management of preeclampsia, which could ultimately improve maternal and fetal outcomes.

OBJETIVO: El estudio tuvo como objetivo determinar el valor de los marcadores de activación plaquetaria en la predicción de la preeclampsia y su gravedad. MÉTODO: Se incluyeron 99 pacientes diagnosticadas con preeclampsia, incluyendo 36 casos graves, y un grupo control de 60 mujeres embarazadas sanas. Se evaluaron diversas variables, como el volumen plaquetario medio, el recuento de plaquetas, el hematocrito plaquetario y la amplitud de distribución plaquetaria. RESULTADOS: Los resultados mostraron que el volumen plaquetario medio y la amplitud de distribución plaquetaria son parámetros valiosos en el diagnóstico y seguimiento de la preeclampsia, aunque no son suficientes para predecir su gravedad. El análisis estadístico reveló que la edad, el volumen plaquetario medio, la amplitud de distribución plaquetaria, la semana de gestación y los puntajes de Apgar al primer y quinto minuto fueron significativamente diferentes en el grupo de preeclampsia en comparación con el grupo control. CONCLUSIONES: En conclusión, estos resultados sugieren que los marcadores de activación plaquetaria pueden ser útiles para el diagnóstico y seguimiento de la preeclampsia, y que el volumen plaquetario medio y la amplitud de distribución plaquetaria, por ser parámetros económicos y accesibles, podrían ayudar a predecir, diagnosticar y manejar esta complicación durante el embarazo.

Are antral follicle count and serum anti-Mullerian hormone level, as reliable markers of ovarian reserve, affected by UV radiation?

ObjectiveWe aimed to assess whether ovarian reserve test including serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH) levels, and antral follicle count (AFC) which are ovarian reserve markers are affected by ultraviolet (UV) radiation or not.MethodsWomen between the ages of 25 and 40 who served as flight crew constituted the study population in this prospective case-control study. Age-matched women having no risk factor for low ovarian reserve were selected as control group. Participants were compared according to age, duration in profession, and ovarian reserve markers.ResultsA total of 134 patients were included: 66 participants in study group and 68 participants in control group. Serum AMH levels and AFC were found to be significantly lower while serum FSH and E2 levels were significantly higher in the study group. This difference was found to be more significant, especially in the advanced age group. When the participants were classified according to their working time, lower ovarian reserve was observed in women with longer working time.DiscussionWorking for a while in the air and being closer to the sun have negative effects on ovarian functions. Preventive measures may be taken earlier in flight crew than those in the normal population to prevent the decline of ovarian functions and possible conceiving problems.