UNASSIGNED: The c-met proto-oncogene (MET) serves as a significant primary oncogenic driver in non-small cell lung cancer (NSCLC) and has the potential to fuse with other genes, such as KIF5B, although it occurs infrequently. Only a limited number of reported cases have examined the clinical efficacy of crizotinib in patients with KIF5B-MET gene fusion, with no known data regarding acquired resistance to crizotinib and its potential mechanisms. In this report, we present the clinical progression of a female patient diagnosed with NSCLC and harboring a KIF5B-MET gene fusion.
UNASSIGNED: The patient initially exhibited partial response to first-line crizotinib treatment, albeit for a short duration and with limited efficacy. Subsequent disease progression revealed the emergence of a secondary MET mutation, specifically MET Y1230H, leading to acquired resistance to crizotinib.
UNASSIGNED: The reporting of this case is imperative for informing clinical practice, given the uncommon occurrence of NSCLC with MET fusion, displaying responsiveness to MET tyrosine kinase inhibitor therapy, as well as the emergence of the secondary Y1230H alteration as a potential resistance mechanism.

UNASSIGNED: Acute myocardial infarction (AMI) is a severe acute coronary syndrome, demonstrating a trend toward affecting younger individuals in recent years. The association between early-onset myocardial infarction and single nucleotide polymorphism necessitates further exploration and evaluation.
UNASSIGNED: We present a case of a patient experiencing early-onset and recurrent myocardial infarction. The patient underwent stent implantation for myocardial infarction at the age of 53 and subsequently encountered two more myocardial infarctions within a span of 16 years. Following interventional therapy, genetic testing was conducted to assess the efficacy of subsequent anti-heart failure medications, with the aim to preemptively address heart failure risks. Genetic testing revealed a mutation in the angiotensin-converting enzyme (ACE) gene (rs577350502, g.63488533C>A), characterized by an intron-deletion single nucleotide variant.
UNASSIGNED: While this variant has not been previously reported to be associated with any specific disease, we hypothesize that it may contribute to the susceptibility and risk of myocardial infarction and coronary heart disease in the patient under consideration. This observation underscores the significance of investigating the insertion/deletion polymorphisms of the ACE gene in the context of AMI and emphasizes the necessity for further validation of this variant and other genetic markers associated with AMI in related diseases.

Autosomal Dominant Mental Retardation Type 7 is a disorder caused by pathogenic variants in the DYRK1A gene. Clinical features associated with this gene mutation include focal dysmorphism, developmental delay, and epilepsy. In this report, we present a case of an 8-year-old boy with a DYRK1A gene mutation, whose clinical manifestations underscore the rarity and clinical challenges of this genetic condition. The patient is a known case of global developmental delay with intractable epilepsy on multiple anti-epileptic medications. Upon examination, the patient showed delayed developmental milestones, hypotonia with brisk deep tendon reflexes, as well as dysmorphic features in the form of microcephaly, deep-set eyes, prominent ears, and a short nose. MRI was done, and findings were suggestive of a DYRK1A gene mutation. The diagnosis was later confirmed by Whole Exome Sequencing (WES). Our report aims to contribute to the growing knowledge about DYRK1A mutations, facilitating a better understanding of the associated clinical features and implications for patient care.

We performed the next-generation sequencing (NGS) analysis of a rare grade 1 brain meningioma (angiomatous type) and a common grade 1 spinal meningioma (psammomatous type) and compared their mutation profiling. The data were analysed using the Ion Reporter 5.16 programme (Thermo Fisher Scientific, Waltham, MA). Sequencing analysis identified 10 novel variants and two previously reported variants that were common between these two tumours. Nine variants were missense, which included an insertion in EGFR c.1819_1820insCA, causing frameshifting, and a single nucleotide deletion in HRAS and HNF1A genes, causing frameshifting in these genes. These were common variants identified for both tumours. Also, 10 synonymous variants and 10 intronic variants were common between these two tumours. In intronic variants, two were splice site_5\' variants (acceptor site variants). Typical of the angiomatous type tumour, there were 11 novel and six previously reported variants that were not found in the psammomatous tumour; three variants were synonymous, 11 were missense mutations, and three were deletions causing frameshifting. The deletion variants were in the SMARCB1, CDH1, and KDR genes. In contrast, eight novel and five previously reported variants were found in the psammomatous meningioma tumour. In this tumour, two variants were synonymous: a deletion causing a frameshifting in [(c.3920delT; p. (Ile1307fs)], and a two-base pair insertion and deletion (INDEL) [(c.3986_3987delACinsGT; p. (His1329Arg)] both in the APC gene were also found. Among our findings, we have identified that ALK, VHL, CTNNB1, EGFR, ERBB4, PDGFRA, KDR, SMO, ABL1, HRAS, ATM, HNF1A, FLT3, and RB1 mutations are common for psammomatous meningioma and angiomatous tumours. Variants typical for angiomatous (brain) meningioma are PIK3CA, KIT, PTPN11, CDH1, SMAD4, and SMARCB1; the variants typical for psammomatous meningioma are APC, FGFR2, HNF1A, STK11, and JAK3. The RET splice variant (c.1880-2A>C) found in both meningioma tumours is reported (rs193922699) as likely pathogenic in the Single Nucleotide Polymorphism Database (dbSNP). All missense variants detected in these two meningiomas are found in the cancer-driver genes. The eight variants we found in genes such as EGFR, PDGFRA, SMO, FLT3, PIK3CA, PTPN11, CDH1, and RB1 are glioma-driver genes. We did not find any mutations in genes such as BRAF, IDH1, CDKN2A, PTEN, and TP53, which are also listed as cancer-driver genes in gliomas. Mutation profiling utilising NGS technology in meningiomas could help in the accurate diagnosis and classification of these tumours and also in developing more effective treatments.

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Multiple morphological changes in two or more sites of concurrent multifocal mucinous lesions in the female genital tract are indicative of SMMN-FGT, which is unrelated to high-risk HPV infection. MUC6 and HIK-1083 showed positive characteristic immunohistochemistry. Seldom is the condition described. Here we describe an SMMN-FGT patient who also had lung metastases and STK11/KRAS gene mutations. Based on the current researches, we hypothesize that SMMN-FGT is closely associated with the development of cervical gastric adenocarcinoma.

BACKGROUND: Ehlers-Danlos syndromes (EDS) comprise a rare variety of genetic disorders, affecting all types of collagen. Herein, we describe a case of the vascular type of EDS, with coexisting segmental absence of intestinal musculature, while simultaneously performing a narrative review of the existing literature.
METHODS: A 23-year-old male patient with a history of multiple abdominal operations due to recurrent bowel perforations and the presence of a high-output enterocutaneous fistula was admitted to our surgical department for further evaluation and treatment. After detailed diagnostic testing, the diagnosis of vascular-type EDS (vEDS) was made and a conservative therapeutic approach was adopted. In addition, a comprehensive review of the international literature was carried out by applying the appropriate search terms.
RESULTS: The diagnosis of vEDS was molecularly confirmed by means of genetic testing. The patient was treated conservatively, with parenteral nutrition and supportive methods. Thirty-four cases of bowel perforation in vEDS have been reported so far. Interestingly, this case is the second one ever to report co-existence of vEDS with Segmental Absence of Intestinal Musculature.
CONCLUSIONS: Establishing the diagnosis of vEDS promptly is of vital significance in order to ensure that patients receive appropriate treatment. Due to initial non-specific clinical presentation, EDS should always be included in the differential diagnoses of young patients with unexplained perforations of the gastrointestinal tract.

BACKGROUND: Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels. Congenital lymphangiectasia can affect various organ systems; however, it frequently occurs in the lungs accompanied with unexplained pleural effusion. Further, it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities. However, after birth the newborn rapidly develops respiratory distress that quickly deteriorates. Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease. We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes, which have not been reported previously.
METHODS: We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth. An autopsy revealed lymphangiectasia of the organ systems. Further, whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes, ADAMTS3 and FLT4, and Sanger verification revealed similar lesions in the mother with no symptoms.
CONCLUSIONS: Considering the presented case, obstetricians should observe unexplained foetal pleural effusion, and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.

Inflammatory bowel disease (IBD) is a heterogeneous group of disorders associated with environmental triggers and dysregulated immune responses resulting in chronic, recurrent intestinal inflammation. Very early-onset IBD (VEO-IBD) refers to patients with symptoms or diagnosis before the age of 6 years and is widely thought to be associated with monogenic mutations. Traditional drug therapy is often ineffective in this patient population, while hematopoietic stem cell transplantation (HSCT) represents the definitive cure for patients with gene mutations.
We report a case of VEO-IBD associated with a monogenic mutation in a 2-year-old girl presenting mainly with gastrointestinal symptoms, including recurrent hematochezia and abdominal pain for more than 3 months. A gastroscopy revealed erosive gastritis and bulbar duodenitis, while a colonoscopy indicated erosive colitis. Abnormal results were obtained from the dihydrohodamine (DHR) assay and immunoglobulin testing. Whole-exome sequencing identified a heterozygous and de novo nonsense mutation (c.388 C > T; p.R130X) in the CYBB gene leading to deficiency of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) (encoded by CYBB), a critical component of phagocytes. HSCT was performed successfully, and the DHR assay showed that normal neutrophil function was restored. Six months after HSCT, clinical remission was observed, and a repeat colonoscopy revealed intestinal mucosal healing was attained.
Patients with CYBB mutations often develop recurrent or severe bacterial or fungal infections, mostly in the lungs, skin, lymph nodes, and liver. Here, we report on a young female child with CYBB mutations presenting predominantly with gastrointestinal symptoms. This study explores the mechanisms of inflammatory bowel disease caused by a monogenic mutation in CYBB to improve early diagnosis and effective treatment rates of this patient population.

UNASSIGNED: The widespread occurrence of syphilis remains a global public health problem. Although penicillin has been recommended as the first-line therapy for syphilis for more than 70 years, treatment failure occurs in 10-20% of patients with early syphilis. Recent studies have reported varied single-nucleotide polymorphisms (SNPs) of Treponema pallidum related to penicillin resistance. The clinical relevance of these SNPs to treatment failure in patients with early syphilis is unresolved. In this work, a protocol is developed to evaluate the association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of T. pallidum.
UNASSIGNED: A multicentre nested case-control study is designed, and patients who are diagnosed with early syphilis and treated with penicillin will be recruited for the study cohort. Before the first treatment, baseline information and biological specimens will be collected from the subjects, and serological tests for syphilis will be performed. Each participant will be followed up at 1, 3, 6, 9, and 12 months after the first treatment, and the clinical manifestations and serum non-treponemal test titres will be evaluated at each follow-up. Patients who will fail treatment are defined as cases, and those who will respond to treatment are defined as controls. Tests for SNPs related to penicillin-binding proteins and Tp47 will be performed in these cases and controls. Survival analysis is used performed to identify gene mutations of T. pallidum related to penicillin resistance and their combinations associated with treatment failure.
UNASSIGNED: This protocol provides a practical clinical study design that illustrates the role of gene mutations of T. pallidum related to penicillin resistance in the treatment outcome of patients with early syphilis.