Surgery for long tubular intestinal duplication with massive hemorrhage: a case report and literature review.

BACKGROUND: Long tubular duplication is a rare congenital intestinal disease, that can lead to emergency situations marked by massive hemorrhage. However, preoperative diagnosis and surgical treatment are challenging. This report presents preoperative images and details a surgical procedure for long tubular intestinal duplications with massive hemorrhage. CASE PRESENTATION: A 3-year-old boy presented to the emergency department with melena. Despite undergoing a Tc-99m pertechnetate scintigraphy one year prior, which revealed nonspecific findings with enhancement of some parts of the intestine, enhanced abdominal CT revealed an edematous small intestine with luminal extravasation. The patient received a transfusion of red blood cells; however, his hemoglobin level did not improve. Arterial angiography and double-balloon endoscopy revealed no remarkable findings. Exploratory laparotomy revealed a long tubular duplication in half of the small intestine. Utilizing the Wrenn procedure, we successfully removed all duplicate mucosa. Pathological findings showed that almost all duplications contained gastric mucosa and revealed an ulcer with a ruptured arterial vessel. His symptoms were resolved, and the hemoglobin level stabilized. At 2 months postoperatively, no surgical complications were present. CONCLUSIONS: Effective management of long tubular duplications with massive hemorrhage involves timely application of the Wrenn procedure. Recognition of specific imaging findings is crucial to prompt exploratory laparotomy, ensuring optimal outcomes and preventing delays in treatment.

Nonsense-associated altered splicing of MAP3K1 in two siblings with 46,XY disorders of sex development.

Although splicing errors due to single nucleotide variants represent a common cause of monogenic disorders, only a few variants have been shown to create new splice sites in exons. Here, we report an MAP3K1 splice variant identified in two siblings with 46,XY disorder of sex development. The patients carried a maternally derived c.2254C>T variant. The variant was initially recognized as a nonsense substitution leading to nonsense-mediated mRNA decay (p.Gln752Ter); however, RT-PCR for lymphoblastoid cell lines showed that this variant created a new splice donor site and caused 39 amino acid deletion (p.Gln752_Arg790del). All transcripts from the variant allele appeared to undergo altered splicing. The two patients exhibited undermasculinized genitalia with and without hypergonadotropism. Testosterone enanthate injections and dihydrotestosterone ointment applications yielded only slight increase in their penile length. Dihydrotestosterone-induced APOD transactivation was less significant in patients' genital skin fibroblasts compared with that in control samples. This study provides an example of nonsense-associated altered splicing, in which a highly potent exonic splice site was created. Furthermore, our data, in conjunction with the previous data indicating the association between MAP3K1 and androgen receptor signaling, imply that the combination of testicular dysgenesis and androgen insensitivity may be a unique phenotype of MAP3K1 abnormalities.

Rare variant of the epigenetic regulator SMCHD1 in a patient with pituitary hormone deficiency.

Isolated hypogonadotropic hypogonadism (IHH), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) constitute a disease spectrum whose etiology remains largely unknown. This study aimed to clarify whether mutations in SMCHD1, an epigenetic regulator gene, might underlie this disease spectrum. SMCHD1 is a causative gene for Bosma arhinia microphthalmia syndrome characterized by arhinia, microphthalmia and IHH. We performed mutation screening of SMCHD1 in patients with etiology-unknown IHH (n = 31) or CPHD (n = 43, 19 of whom also satisfied the SOD diagnostic criteria). Rare variants were subjected to in silico analyses and classified according to the American College of Medical Genetics and Genomics guidelines. Consequently, a rare likely pathogenic variant, p.Asp398Asn, was identified in one patient. The patient with p.Asp398Asn exhibited CPHD, optic nerve hypoplasia, and a thin retinal nerve fiber layer, and therefore satisfied the criteria of SOD. This patient showed a relatively low DNA methylation level of the 52 SMCHD1-target CpG sites at the D4Z4 locus. Exome sequencing for the patient excluded additional variants in other IHH/CPHD-causative genes. In vitro assays suggested functional impairment of the p.Asp398Asn variant. These results provide the first indication that SMCHD1 mutations represent a rare genetic cause of the HH-related disease spectrum.

Random X chromosome inactivation in patients with Klinefelter syndrome.

BACKGROUND: X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10-12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype. METHODS: We examined XCI ratios in 18 KS patients through DNA methylation analysis for the polymorphic trinucleotide locus in the AR gene. The results of the KS patients were compared to previous data from healthy young women. RESULTS: XCI ratios in KS patients followed a normal distribution. Skewed XCI was observed in two patients, one of whom exhibited extremely skewed XCI. The frequencies of skewed and extremely skewed XCI in the KS cohort were comparable to those in healthy women. CONCLUSION: This study confirmed the rarity of skewed XCI in KS patients. These results indicate that the presence of a supernumerary X chromosome during the cleavage and early blastocyst stages does not affect the developmental tempo of embryos. Our data deserve further validation.