Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

WT1 mutation as a cause of 46 XY DSD and Wilm's tumour: a case report and literature review.

AIM: The Wilms' Tumour gene is thought to have tumour suppressor activity and to play an important role in nephrogenesis, genitourinary development, haematopoiesis and sex determination. WT1 mutations will impair gonadal and urinary tract development and have been demonstrated to cause syndromes of WAGR, Denys-Drash and Fraiser. METHODS: To elucidate the role of constitutional mutations of WT1, in the expression of the different clinical feature, we describe a 14-year-9-month nonmosaic XY sex-reversed woman with pure gonadal dysgenesis (46, XY karyotype, completely female external genitalia, normal Mullerian ducts, absence of Wolffian ducts, streak gonads) who had right kidney removed at 7 months of age because of Wilms' tumour and was diagnosed as secondary thrombocytopenia (Plt 60-80 × 10(9) /L) since she was 4 years old. We sequenced the genomic DNA of all the 10 exons of the WT1 in which mutations may occur in proposita. RESULTS: A new de novo insertion mutation in the first exon was found. A 'GCCGCCTCACTCC' is inserted between codon 138 and 139, resulting in the creation of a stop codon and a truncated protein. CONCLUSION: The present data provide further evidence to support the role of WT1 in diverse cellular functions.