ABSTRACT
46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.
ABSTRACT
<p><b>OBJECTIVE</b>To describe the outcomes and recurrence of autoimmune hepatitis (AIH) after liver transplantation.</p><p><b>METHODS</b>Clinical data of 16 patients with AIH who underwent liver transplantation were analyzed retrospectively. The postoperative cumulative survival rate of the patients was calculated. The postoperative rejections and AIH recurrence were analyzed. The Kaplan-Meier method was used for statistical analysis of survival.</p><p><b>RESULTS</b>All patients were female, with an average age of 52.6 years (range: 41-66 years), and an average MELD score of 21.4. According serological analysis, 15 patients were AIH type 1 and 1 patient was AIH type 2. Three patients died, including 2 of pulmonary infection and 1 of graft dysfunction.The 1-, 2-and 5-year cumulative survival rates were 93.8%, 87.1% and 79.1%, respectively. Five cases (31.3%) of recurrent AIH were diagnosed based on histological evidence. Acute rejection occurred in 6 (37.5%) patients, and de novo HBV infection occurred in 1 (6.3%) patient.</p><p><b>CONCLUSION</b>Liver transplantation is an effective treatment for end-stage AIH. Recurrence and rejection were commonly associated with AIH, but did not negatively impact patient survival.</p>