RESUMO
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidadesRESUMO
This study evaluated COVID-19-related intrusive thoughts and associated ritualistic behaviors (CITRB). From March to May 2020, 1,118 Chinese high school students, college students, psychiatric outpatients, and community members completed a survey assessing CITRB, generalized anxiety, depression, somatization, obsessive-compulsive symptoms, and pandemic-related disruptions. Overall, participants reported mild to moderate CITRB, although certain thoughts/behaviors were more frequently endorsed, such as repeatedly telling others to take precautions against COVID-19 and checking COVID-19-related news. Being male, younger, a health-care worker, or in isolation/quarantine was associated with CITRB severity in community members. Obsessive-compulsive symptom severity, depression, somatic symptoms, and anxiety were associated with CITRB severity, although only obsessive-compulsive symptoms were uniquely associated with CITRB. This study provided evidence for the construct of CITRB, which may help mental health providers identify the nature and sources of COVID-19-related distress for some individuals as well as serve as a framework for evaluating obsessive-compulsive symptoms specific to large-scale crises.
Assuntos
COVID-19 , Transtornos Mentais , Saúde Mental , Feminino , Humanos , Masculino , Ansiedade , Transtornos de Ansiedade , Povo Asiático , COVID-19/complicações , COVID-19/psicologia , Inquéritos Epidemiológicos , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/psicologia , Angústia Psicológica , ChinaRESUMO
OBJECTIVES: The aim of this study was to determine the incidence of perioperative respiratory complications in children following tonsillectomy with cold and hot dissection surgical techniques. STUDY DESIGN: The study was a retrospective cohort study. SETTING: Retrospective chart review was performed for all children presenting for a tonsillectomy at Texas Children's Hospital from November 2015 to December 2017. METHODS: Pre- and intraoperative patient factors, including surgical technique with cold or hot dissection (electrocautery or radiofrequency ablation), and perioperative anesthetic factors were collected to determine the incidence of perioperative respiratory complications. RESULTS: A total of 2437 patients underwent a tonsillectomy at Texas Children's Hospital from November 2015 to December 2017. The incidence of perioperative respiratory complications was 20.0% (n = 487). Sickle cell disease, cardiac disease, reactive airway disease, pulmonary disease, age >2 and <3 years, and obesity, defined as a body mass index >95th percentile for age, were significant for overall perioperative respiratory complications. There was no difference in the incidence of perioperative respiratory complications in children undergoing tonsillectomy by cold or hot dissection. CONCLUSION: Perioperative respiratory complications following tonsillectomy are more affected by patient factors than surgical technique.