Patients with Marfan syndrome have a constellation of clinical features and a heterogeneous phenotype. The purpose of this study is to report a 47-year-old male patient with an unusual variant in the FBN1 gene causing Marfan syndrome. The patient with musculoskeletal, cardiovascular, and ocular findings compatible with Marfan syndrome had an unusual pathogenic mutation on the FBN1 gene. The patient was examined by at least one of the authors (NJI). The patient\'s clinical findings were compatible with Marfan syndrome. Our patient had a unique mutation in the FBN1 gene (c.8054A>G p.His2685Arg) located on exon 65. Next-generation sequencing was done using the Invitae panel. This variant was categorized as one of uncertain significance. This patient\'s variant on the FBN1 gene leading to the syndrome has scant data associated with it and this is the first time it is reported from Puerto Rico.

Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP-D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by pathogenetic variants in FBN1. Here, we report a patient with type 2 diabetes mellitus, AVP-D, and Marfan syndrome. Although the coexistence of type 2 diabetes mellitus and AVP-D is rare, for those patients with type 2 diabetes mellitus, the existence of AVP-D should be considered when polyuria is not in accordance with the blood glucose levels, especially for those with a low urine specific gravity. Specific symptoms or signs help to identify Marfan syndrome early, and genetic testing of the FBN1 pathogenetic variant helps to make a definitive diagnosis.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder due to pathogenic variants in Fibrillin-1 (FBN1) affecting nearly one in every 10,000 individuals. We report a 16-month-old female with early-onset MFS heterozygous for an 11.2 kb de novo duplication within the FBN1 gene. Tandem location of the duplication was further confirmed by optical genome mapping in addition to genetic sequencing and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. As the vast majority of pathogenic variants associated with MFS are point mutations, this expands the landscape of known FBN1 pathogenic variants and supports consistent use of genetic testing strategies that can detect large, indel-type variants.

BACKGROUND Inherited deficiencies in the FBN1 gene, which encodes fibrillin-1, result in Marfan syndrome, an autosomal dominant connective tissue disorder that is associated with aortic root dilatation and predisposes to aortic dissection. This report is of a 37-year-old woman presenting at 39 weeks of pregnancy with acute thoracic aortic dissection due to previously undiagnosed FBN1-related Marfan syndrome. This case report aims to illustrate the challenges in the diagnosis and in the peri-operative management of acute aortic dissection during pregnancy. CASE REPORT A healthy 37-year-old woman at 39 weeks of gestation presented to our hospital with dyspnea and chest pain. Initial evaluation for pulmonary embolism with chest computed tomography was unrevealing. The patient was admitted to the intensive care unit for further management. Overnight, her clinical conditions deteriorated, and a transthoracic echocardiography was obtained, demonstrating an acute ascending aortic dissection. She emergently underwent a successful combined cesarean section and ascending aortic dissection repair, with no immediate complications. On postoperative day 4 she developed cardiac tamponade, for which she underwent emergent mediastinal exploration. She was discharged home on postoperative day 10. A month later she completed genetic testing, which revealed a pathogenic mutation in the FBN1 gene, consistent with a molecular diagnosis of Marfan syndrome. CONCLUSIONS This report has shown that FBN1-related Marfan\'s syndrome has a variable clinical presentation that can include life-threatening aortic dissection during pregnancy. Successful diagnosis and management of these patients is challenging and requires multidisciplinary expertise, including confirmation of the diagnosis by a clinical geneticist.

Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder affecting the cardiovascular, skeletal, and ophthalmic systems. This report aimed to describe a novel genetic background and treatment prognosis of MFS.
A proband was initially diagnosed with bilateral pathologic myopia and suspected MFS. We performed whole exome sequencing and found a pathogenic nonsense FBN1 mutation in the proband, which confirmed the diagnosis of MFS. Notably, we identified a second pathogenic nonsense mutation in SDHB, which increased the risk of tumours. In addition, the proband karyotype was X trisomy, which may cause X trisomy syndrome. At the 6-month follow-up after posterior scleral reinforcement surgery, the proband\'s visual acuity improved significantly; however, myopia was still progressing.
We report a rare case of MFS with a X trisomy genotype, a mutation in FBN1 and a mutation in SDHB for the first time, and our findings could be helpful for the clinical diagnosis and treatment of this disease.

BACKGROUND: Studies have suggested that serum asprosin and irisin were involved in type 2 diabetes mellitus (T2DM) and obesity. This study evaluated circulating levels of asprosin and irisin and their associations with anthropometric and metabolic parameters, especially the visceral fat area (VFA) in T2DM patients with abdominal obesity (AO).
METHODS: In this case-control study, 131 patients with T2DM were grouped into an AO group (n = 68) and a non-AO group (NAO) (n = 63) based on their VFA. Anthropometric and metabolic parameters as well as serum asprosin and irisin levels were measured and compared between the 2 groups.
RESULTS: Compared to the NAO group, the AO group had significantly higher serum asprosin and irisin concentrations (3.67 ± 1.76 ng/mL vs. 2.85 ± 0.90 ng/mL, p = 0.001; 154.62 ± 61.87 pg/mL vs. 130.54 ± 34.89 pg/mL, p = 0.008, respectively) and greater VFA (p < 0.001). Serum asprosin in the AO group was positively associated with weight, waist circumference (WC), hipline, body mass index, fasting blood glucose (FBG), glycated haemoglobin (HbA1c), VFA, subcutaneous fat area, and total abdominal fat area (TAFA), and the serum irisin concentration in the AO group was positively correlated with WC, waist-to-hip ratio (WHR), VFA, and TAFA and negatively correlated with FBG. Stepwise logistic regression analysis suggested that FBG and VFA were independent factors positively associated with serum asprosin, and that FBG was independently, negatively associated with serum irisin, while VFA was independently, positively associated with serum irisin.
CONCLUSIONS: Elevated serum asprosin and irisin levels in T2DM patients with AO and their correlations with other metabolic parameters suggest that both are potential therapeutic agents/targets in treating obesity and its related disorders.

Marfan syndrome (MFS), an inherited connective tissue disorder, is caused by a mutation in the FBN1 gene. MFS is characterized by manifestations in the musculoskeletal system (joint laxity, scoliosis), the cardiovascular system (aortic dilation), and the ocular system (ectopic lens). We report a case of a 37-year-old male with a genetically confirmed MFS. His mother and brother were also both confirmed cases of MFS. While the patient exhibited the characteristic physical features of MFS in general appearance, he did not show any cardiac manifestations of the disease. This report highlights a case of the familial occurrence of MFS and emphasizes the importance of recognizing the forme fruste of MFS.

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR. We identified a novel pathogenic mutation (c.8051+1G>C) in the splice site of exon 64 of the FBN1 gene in an MFS-pedigree. This mutation was confirmed to cause two different truncated transcripts (entire exon 64 skipping; partial exon 64 exclusion). We also systematically summarized previously reported transcriptional studies of pathogenic splice-altering mutations in the FBN1 gene to investigate the clinical and transcriptional consequences. In conclusion, we reported for the first time that a splice-altering mutation in the FBN1 gene leads to two abnormal transcripts simultaneously.

BACKGROUND: Fibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient\'s characteristics.
METHODS: DNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient\'s age and body mass index (BMI).
RESULTS: Among the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35-0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°).
CONCLUSIONS: Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

Marfan syndrome is a rare autosomal dominant disorder of the connective tissue. It results in a mutation in the Fibrillin-1 protein gene. We present a case of  Marfan\'s syndrome in a young adult with life-threatening, sudden onset of chest pain secondary to a non-ST elevation myocardial infarction (NSTEMI) in the setting of an aortic pseudoaneurysm. Taking into consideration potential life-threatening underlying processes, a thorough and detailed methodology must be undertaken when encountering chest pain in a Marfan\'s syndrome patient. This case highlights the importance of utilizing a multi-disciplinary approach to the complexities of Marfan syndrome.