Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Waardenburg syndrome type 4C due to heterozygous deletion of SOX10 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree featuring congenital profound syndromic deafness and chronic constipation, and provide prenatal diagnosis for a high-risk fetus.@*METHODS@#Whole-exome sequencing was carried out to analyze the sequences of genes associated with hereditary deafness, and multiplex ligation-dependent probe amplification (MLPA) was used to verify the candidate variant in the proband's parents and the fetus.@*RESULTS@#The proband was found to have harbored a heterozygous deletion of SOX10, a pathogenic gene associated with Waardenburg syndrome type 4C (WS4C). The same deletion was found in her mother (with profound syndromic deafness and chronic constipation) and the fetus, but not in her father with normal hearing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the SOX10 gene deletion was predicted to be a pathogenic variant (PVS1+PM2_Supporting+PP1+PP4).@*CONCLUSION@#The pedigree was diagnosed with WS4C, which has conformed to an autosomal dominant inheritance. Deletion of the entire SOX10 gene, as a loss-of-function variant, probably underlay its pathogenesis. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.

Mechanism of Shouhui Tongbian Capsules in treating constipation based on network pharmacology and molecular docking / 中国中药杂志

To explore the mechanism of Shouhui Tongbian Capsules in treating constipation by means of network pharmacology and molecular docking approach. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinfoematics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN) were applied to obtain chemical components and potential targets of eight herbs in Shouhui Tongbian Capsules according to the screening principles of oral availability(OB)≥30% and drug-like property(DL)≥0.18. Disease targets relating to constipation were screened out through GeneCards, PharmGkb and other databases, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Shouhui Tongbian Capsules for treating constipation; PPI network of potential targets was constructed using STRING platform, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) pathway data were obtained to conduct enrichment analysis and predict its mechanism of action. Cytoscape 3.6.1 was used to construct a network of "medicinal materials-chemical components-drug targets", and the network topology analysis was carried out on the PPI network to obtain its main components and key targets. Molecular docking between components and key targets of Shouhui Tongbian Capsules verified the accuracy of network pharmacological analysis results. The PPI network analysis showed 92 chemical components, including quercetin, stigmaste-rol, aloe-emodin, rhein, and key targets for instance AKT1, MAPK1, IL6, JUN, TNF and TP53. The enrichment analysis of KEGG screened out 157 signal pathways(P<0.01), mainly involving interleukin 17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, thyroid hormone signaling pathway. Quercetin, resveratrol and lysine with top degree value had a rational conformation in docking site of protein crystal complexes. This study preliminarily showed that various active ingredients in Shouhui Tongbian Capsules could regulate multiple signaling pathways, increase intestinal smoothness and peristalsis function, ensure smooth intestinal lumen, and play a role in treating constipation by acting on key targets, such as AKT1, MAPK1, IL6 and JUN.

Dermatóglifos em crianças com constipação crônica / Dermatoglyphics of children with chronic constipation

RACIONAL: Os dermatóglifos podem ser utilizados na avaliação da transmissão genética de determinadas doenças, sendo controversa na literatura a associação entre o padrão arco e constipação. OBJETIVO: Comparar os padrões de dermatóglifos de crianças com constipação crônica com os de crianças sem constipação e com o hábito intestinal e padrões de dermatóglifos de suas mães. MÉTODOS: Foram estudados três grupos de crianças com idade entre 2 e 12 anos e suas respectivas mães: 35 pacientes com constipação grave, 45 crianças com constipação leve e 51 crianças com hábito intestinal normal, que constituíram o grupo-controle. Preencheu-se ficha padronizada com informações gerais e do hábito intestinal das crianças e de suas mães. Obtiveram-se as impressões digitais das crianças e de suas mães, que foram classificadas em arco, presilha radial, presilha ulnar, verticilo e outros. RESULTADOS: A freqüência do padrão arco foi semelhante nos três grupos estudados: constipação grave (25,7 por cento), constipação leve (28,9 por cento) e controles (23,5 por cento). Hábito intestinal compatível com constipação foi observado em 51,9 por cento (68/131) das mães. Arco foi observado em 35,3 por cento das mães com constipação e em 42,9 por cento das com hábito intestinal normal. Foi observada concordância muito leve entre a ocorrência de constipação na criança e na mãe. CONCLUSAO: Não se observou associação entre a presença de arco e constipação, tanto nas crianças como em suas mães, sendo muito leve a concordância entre a ocorrência de constipação na criança e em suas mães biológicas.