西澤 春紀

BACKGROUND: LHX8 gene encodes a germ cell specific transcription factor that is required for oocyte development. We evaluated two unrelated women with primary infertility who showed reproducible oocyte abnormalities across in vitro fertilization cycles, and we performed genomic and functional assays to clarify the role of LHX8. RESULTS: Whole exome sequencing identified heterozygous loss-of-function variants in LHX8 (NM_001001933.1) in both patients: c.778 C > T (p.Gln260Ter) in family 1 and c.581-1G > A in family 2. Both variants met the American College of Medical Genetics and Genomics criteria for likely pathogenicity. The two patients had high proportions of degenerated or immature oocytes and showed consistent morphologic features, including multiple cytoplasmic vacuoles, impaired zona pellucida function with accumulation of sperm in the perivitelline space, and poor embryo development. The splice site variant was inherited from a fertile mother, which indicates incomplete penetrance. A minigene assay confirmed the use of a cryptic acceptor site that produced a one nucleotide deletion and a frameshift, consistent with loss of function. CONCLUSIONS: These findings expand the phenotypic spectrum of LHX8 related infertility and provide mechanistic evidence that partial reduction of LHX8 activity compromises oocyte quality. Recognition of the characteristic morphology may guide genetic testing and counseling in cases of unexplained infertility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-026-01978-2.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neurodevelopmental disorder caused by CTG repeat expansion in the DMPK gene. Although the clinical classification of DM1 is determined by the CTG repeat length in DMPK, conventional sizing relies on Southern blotting, which is a suboptimal method in prenatal and PGD contexts as it requires large amounts of genomic DNA. We here evaluated the utility of nanopore long read sequencing (LRS) for DM1 diagnosis in these contexts. METHOD: LRS was performed with adaptive sampling or CRISPR/Cas9-mediated enrichment targeting DMPK. The use of whole genome amplified DNA (WGA-DNA) prepared with RepliG was also assessed. RESULTS: Adaptive sampling and Cas9-based LRS enabled detection of both the normal and expanded alleles. Further, LRS with CRISPR/Cas9-mediated enrichment improved efficiency and enabled accurate sizing of expanded CTG repeats exceeding 1000 units. In contrast, the use of whole genome amplified DNA prepared with RepliG did not permit reliable CTG repeat sizing, even when combined with adaptive sampling or CRISPR/Cas9. CONCLUSION: Nanopore sequencing can potentially replace Southern blotting for prenatal DM1 diagnosis, including repeat sizing. However, further improvement is needed for PGD using WGA-DNA.

Renal cell carcinoma is a malignant tumor that is prone to distant metastasis, primarily developing in the lungs, bones, lymph nodes, liver, and brain. Conversely, ovarian metastasis is rare, and its clinical characteristics and optimal treatment strategies remain unestablished. We report two cases with renal cell carcinoma and concomitant ovarian metastasis. Case 1 was of a 52-year-old woman with a metastatic tumor in the left ovary detected 9 years after radical nephrectomy for left-sided clear cell renal cell carcinoma. Case 2 was of a 56-year-old woman with a metastatic tumor in the right ovary detected 15 years after radical nephrectomy for right-sided clear cell renal cell carcinoma. In both cases, preoperative imaging revealed a pelvic tumor with a strong contrast effect. Surgery was performed for diagnosis and treatment of suspected ovarian metastasis from the renal cell carcinoma. Rapid intraoperative diagnosis was performed to determine the surgical approach, and the diagnosis of ovarian metastasis from renal cell carcinoma was made. Subsequently, bilateral adnexectomy was performed, and following pathological examination led to the definite diagnosis of ovarian metastasis from clear cell renal cell carcinoma. Long after radical nephrectomy, ovarian metastasis from the renal cell carcinoma can occur. Therefore, continuous follow-up is important. Complete resection of ovarian metastases from renal cell carcinoma may contribute to improved prognosis; however, more case studies are needed to establish standard treatment.

OBJECTIVES: Hormone replacement therapy (HRT) is considered for ovarian cancer patients who develop menopausal symptoms, dyslipidemia, and osteoporosis due to iatrogenic menopause caused by surgery or anticancer drug treatment. However, there have been few reports on HRT administration methods and those that evaluate cancer recurrence and complications of HRT. METHODS: We examined the administration method, adverse reactions and cancer recurrence in 28 patients who received HRT after ovarian cancer surgery at our hospital. RESULTS: All patients received estradiol monotherapy, and cancer recurrence was observed in four patients (14.3%); adverse reactions included skin eruption in two patients (7.1%), there were no other serious adverse reactions noted. CONCLUSION: The method and duration of HRT administration and the timing of HRT discontinuation remain debated. Thus, a large-scale survey and standardization of HRT administration methods after ovarian cancer surgery in Japan are needed.