[Genetic analysis of a family with BCL11A-related intellectual disability].

OBJECTIVE: To explore the genetic basis for two patients from a family with BCL11A-related intellectual disability (BCL11A-ID). METHODS: Clinical data of the proband and her family members was analyzed. Chromosomal karyotyping analysis, trio-whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were carried out. For the suspected genetic variants, Sanger sequencing was used to verify, and pathogenicity assessment was conducted. RESULTS: The proband and her mother both had intellectual and language impairment, and their fetal hemoglobin (HbF) was significantly elevated. A heterozygous c.1327_c.1328delTC (p.Ser443Hisfs*128) variant was found in exon 4 of the BCL11A gene by WES, which has resulted in truncated expression of the encoded protein, and Sanger sequencing has verified that the variant was inherited from the mother. The variant was not found in related databases. The variant was predicted as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PM2+PP1). No karyotypic abnormality was found in the proband, her parents and brother, and no pathogenic CNVs was found in the proband and her parents. CONCLUSION: The c.1327_c.1328delTC (p.Ser443Hisfs*128) variant may underlay the BCL11A-ID in the proband and her mother. This de novo variant has expanded the mutational spectrum of the BCL11A gene.

Associations between major dietary patterns and anxiety in middle-aged adults in eastern China.

OBJECTIVE: The current study aimed to evaluate the association of major dietary patterns with anxiety in middle-aged adults in eastern China. DESIGN: Dietary intake was assessed using a semi-quantitative FFQ. Binary logistic regression analysis was used to estimate OR and 95 % CI for anxiety according to quartiles of each dietary pattern score. SETTING: Evidence regarding the relationship between dietary patterns and anxiety in the Chinese population is scarce. PARTICIPANTS: The study participants were 1360 Chinese adults aged 45-59 years, who participated in a health survey at the time of periodic check-up in the city of Linyi, Shandong Province, China. RESULTS: Four major dietary patterns were identified by factor analysis: traditional Chinese, western, grains-vegetables and high-salt diets. After adjusting for potential confounders, participants in the highest quartile of the western pattern had greater odds for anxiety, compared with those in the lowest quartile (OR 1·35, 95 % CI 1·000, 3·086, P < 0·05). In contrast, participants in the highest quartile of the grains-vegetables pattern had lower odds for anxiety than did those in the lowest quartile (OR 0·78, 95 % CI 0·574, 1·000, P < 0·05). Moreover, no significant associations were observed between the traditional Chinese and high-salt patterns and the risk of anxiety. CONCLUSIONS: Our findings indicate that the western pattern is associated with an increased risk, and the grains-vegetables pattern is associated with a decreased risk of anxiety.

[Exploration of the pathogenesis for a SRY-negative male with 46,XX disorder of sex development].

OBJECTIVE: To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development (DSD). METHODS: Peripheral blood samples of the patient and his family members were subjected to chromosomal karyotyping, routine PCR, real-time fluorescence quantitative PCR, whole exome sequencing and whole genome sequencing. The data was analyzed with NextGENe software. RESULTS: Both the proband and his brother presented a 46,XX karyotype with negative SRY gene, while their father presented normal phenotype and karyotype with positive SRY gene. No pathogenic variant associated with sex development was detected by whole exome sequencing, while a 243 kb duplication was detected by whole genome sequencing in the 5' upstream region of the SOX9 gene in the proband, his brother and father. The same duplication was not found in his sister and mother. CONCLUSION: The 243 kb duplication at the 5' upstream of the SOX9 gene may predispose to the 46,XX DSD in this family. It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9, and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.