Genetic Analysis of Japanese Children Clinically Diagnosed with Familial Hypercholesterolemia.

AIM: This study aimed to elucidate the gene and lipid profiles of children clinically diagnosed with familial hypercholesterolemia (FH). METHODS: A total of 21 dyslipidemia-related Mendelian genes, including FH causative genes (LDLR, APOB, and PCSK9) and LDL-altering genes (APOE, LDLRAP1, and ABCG5/8), were sequenced in 33 Japanese children (mean age, 9.7±4.2 years) with FH from 29 families. RESULTS: Fifteen children (45.5%) with pathogenic variants in LDLR (eight different heterozygous variants) and one child (3.0%) with the PCSK9 variant were found. Among 17 patients without FH causative gene variants, 3 children had variants in LDL-altering genes, an APOE variant and two ABCG8 variants. The mean serum total cholesterol (280 vs 246 mg/dL), LDL-cholesterol (LDL-C, 217 vs 177 mg/dL), and non-HDL cholesterol (228 vs 188 mg/dL) levels were significantly higher in the pathogenic variant-positive group than in the variant-negative group. In the variant-positive group, 81.3% of patients had LDL-C levels ≥ 180 mg/dL but 35.3% in the variant-negative group. The mean LDL-C level was significantly lower in children with missense variants, especially with the p.Leu568Val variant, than in children with other variants in LDLR, whereas the LDL-altering variants had similar effects on the increase in serum LDL-C to LDLR p.Leu568Val. CONCLUSION: Approximately half of the children clinically diagnosed with FH had pathogenic variants in FH causative genes. The serum LDL-C levels tend to be high in FH children with pathogenic variations, and the levels are by the types of variants. Genetic analysis is useful; however, further study on FH without any variants is required.

Uterus in mixed gonadal dysgenesis was detected by continuous irregular vaginal bleeding.

Disorders of sex development (DSD) are a group of congenital conditions presenting with differences in the chromosomal, gonadal, or anatomic sex development. Evaluating the chromosomes, gonads, and internal and external genitalia of the patients is important for understanding DSD. Furthermore, confirming the presence of a uterus is essential for the assessment of the internal genitalia status. Although the uterus can be identified by ultrasonography, magnetic resonance imaging, or laparoscopy, it may be easily overlooked. Here, we report the case of a patient with mixed gonadal dysgenesis, in whom the presence of a uterus could not be confirmed before the initiation of estrogen replacement therapy despite the performance of various tests. The detection of the uterus was prompted by an atypical genital bleeding. This case implies that physicians may have difficulties identifying the uterus in female patients with DSD before the initiation of estrogen treatment.