Asprosin levels in patients with type 2 diabetes mellitus, metabolic syndrome and obesity: A systematic review and meta-analysis.

BACKGROUND & AIMS: Asprosin is a promising candidate for novel treatments for metabolic-endocrine disorders. The objective of this systematic review and meta-analysis was to consolidate the existing evidence regarding asprosin levels in patients diagnosed with type 2 diabetes (T2D), metabolic syndrome (MetS), and obesity. METHODS: Scopus, Embase, PubMed, Ovid/Medline, and Web of Science were systematically searched without restrictions. We only used the standardized mean differences (SMD) with their 95 % confidence intervals (95 % CI) as the effect measure. A random-effects model (DerSimonian and Laird method) was used for the meta-analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale and Newcastle-Ottawa Scale for Cross-Sectional Studies. RESULTS: Twenty-six studies (n = 3,787) were included in the meta-analysis. Participants with T2D had higher asprosin values than those without T2D (SMD: 1.64; 95 % CI: 1.08-2.21; I2 = 97 %). Patients with MetS had higher asprosin levels compared to those without MetS (SMD: 0.99; 95 % CI: 0.34-1.64; I2 = 96 %). Patients with obesity had higher asprosin levels than participants without obesity (SMD: 1.49; 95 % CI: 0.23-2.76; I2 = 98 %). CONCLUSIONS: Asprosin is significantly higher in patients with either T2D, MetS, or obesity, compared with controls.

The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders.

Marfan syndrome (MFS) is a multisystem genetic disorder with over 3000 mutations described in the fibrillin 1 (FBN1) gene. Like MFS, other connective tissue disorders also require a deeper understanding of the phenotype-genotype relationship due to the complexity of the clinical presentation, where diagnostic criteria often overlap. Our objective was to identify mutations in patients with connective tissue disorders using a genetic multipanel and to analyze the genotype-phenotype associations in a cohort of Mexican patients. We recruited 136 patients with MFS and related syndromes from the National Institute of Cardiology. Mutations were identified using next-generation sequencing (NGS). To examine the correlation between mutation severity and severe cardiovascular conditions, we focused on patients who had undergone Bentall-de Bono surgery or aortic valve repair. The genetic data obtained allowed us to reclassify the initial clinical diagnosis across various types of connective tissue disorders. The transforming growth factor beta receptor 2 (TGFBR2) rs79375991 mutation was found in 10 out of 16 (63%) Loeys-Dietz patients. We observed a high prevalence (65%) of more severe mutations, such as frameshift indels and stop codons, among patients requiring invasive treatments like aortic valve-sparing surgery, Bentall and de Bono procedures, or aortic valve replacement due to severe cardiovascular injury. Although our study did not achieve precise phenotype-genotype correlations, it underscores the importance of a multigenetic panel evaluation. This could pave the way for a more comprehensive diagnostic approach and inform medical and surgical treatment decision-making.

Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome.

Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.

Traboulsi syndrome without features of Marfan syndrome caused by a novel homozygous ASPH variant associated with a heterozygous FBN1 variant.

BACKGROUND: Traboulsi syndrome is a rare disease clinically characterized by facial dysmorphism, abnormal spontaneous filtering blebs, ectopia lentis (EL) and multiple anterior segment abnormalities. MATERIAL AND METHODS: An 18-year-old female was referred to the Emergency Service of Hospital São Geraldo (HSG) claiming decreased right eye (RE) visual acuity associated with ocular pain that was noticed approximately 2 months earlier. She underwent a complete ophthalmic and physical examination including hands, ankle, wrist and chest X-ray, abdominal ultrasound, echocardiogram and genetic analysis (whole-exome sequencing). RESULTS: The ophthalmic examination revealed a high myopia with spherical equivalent of - 9.50 D and best corrected visual acuity (BCVA) of 20/60 in RE and - 9.25 D with BCVA of 20/30 in the left eye (LE). Slit-lamp examination showed normal conjunctiva in both eyes (BE) and a superior-temporal cystic lesion in RE and nasal in LE; the flat anterior chamber in BE with the transparent crystalline lens touches the central corneal endothelium in the RE. Fundoscopy suggested glaucoma as the cup/disc ratio was 0.7, although the intraocular pressure (IOP) was 10 mmHg in BE without medication. Validation of data from whole exome demonstrated a novel splicing homozygous pathogenic variant (PV) (c.1765-1G>A) of the ASPH gene as well as a heterozygous variant of unknown significance (VUS) of the FBN1 gene (c.6832C>T). CONCLUSION: We here report a novel splice-affecting homozygous pathogenic variant in the ASPH gene that was detected in a Brazilian patient with clinical features of Traboulsi syndrome.

Exome Sequencing Identifies Genetic Variants Associated with Extreme Manifestations of the Cardiovascular Phenotype in Marfan Syndrome.

Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 (FBN1) gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal features and aortic root aneurysm and dissection. Although dissection of the ascending aorta is the main cause of mortality in MFS, the clinical course differs considerably in age of onset and severity, even among individuals who share the same causative variant, suggesting the existence of additional genetic variants that modify the severity of the cardiovascular phenotype in MFS. We recruited MFS patients and classified them into severe (n = 8) or mild aortic phenotype (n = 14) according to age of presentation of the first aorta-related incident. We used Exome Sequencing to identify the genetic variants associated with the severity of aortic manifestations and we performed linkage analysis where suitable. We found five genes associated with severe aortic phenotype and three genes that could be protective for this phenotype in MFS. These genes regulate components of the extracellular matrix, TGFß pathway and other signaling pathways that are involved in the maintenance of the ECM or angiogenesis. Further studies will be required to understand the functional effect of these variants and explore novel, personalized risk management and, potentially, therapies for these patients.

Association of FBN1 polymorphism with susceptibility of adolescent idiopathic scoliosis: a case-control study.

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°). CONCLUSION: Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

Serum asprosin level in different subtypes of polycystic ovary syndrome: a cross-sectional study.

OBJECTIVE: Polycystic ovary syndrome can be divided into different subtypes, including insulin resistance and hyperandrogenism. The aim of this study was to investigate the relationship between serum asprosin levels and polycystic ovary syndrome subtypes. METHODS: A total of 93 women with polycystic ovary syndrome and 77 healthy women as controls were selected for this study. The clinical and laboratory data were compared between the Polycystic ovary syndrome group and the control group. The Polycystic ovary syndrome group was further divided into subgroups: (1) women with or without hyperandrogenism (polycystic ovary syndrome hyperandrogenism and Polycystic ovary syndrome none-hyperandrogenism, respectively) and (2) women with or without insulin resistance (polycystic ovary syndrome insulin resistance and Polycystic ovary syndrome none-insulin resistance, respectively). Serum asprosin was measured by using enenzyme-linked immunosorbent assay. RESULTS: Serum asprosin levels showed no significant difference between the polycystic ovary syndrome and control groups. However, it was significantly lower in the Polycystic ovary syndrome HA and insulin resistance groups compared with the respective Polycystic ovary syndrome none-hyperandrogenism and none-insulin resistance groups (p<0.05). In the Polycystic ovary syndrome group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, homeostatic model assessment of insulin resistance, and triglycerides. After adjusting for body mass index, the correlations were not significant, and asprosin was only positively correlated with prolactin (prolactin; r=0.426, p<0.001). CONCLUSION: Our study shows that women with polycystic ovary syndrome hyperandrogenism or insulin resistance exhibit significantly lower serum asprosin levels compared with controls, and the lower asprosin level directly correlated with prolactin level.

Generation of genetically modified human induced pluripotent stem cell lines harboring haploin sufficient or dominant negative variants in the FBN1 gene.

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. To investigate the molecular mechanisms of pathogenesis for the syndrome, we genetically modified the FBN1 gene in a line of induced pluripotent stem cells (hiPSCs) derived from a healthy donor using the CRISPR/Cas9 gene editing technology. The sublines described here were characterized according to established criteria and were shown to maintain pluripotency, three germ layer differentiation potential and genomic integrity. These clones can now be used to better understand the pathogenesis of MFS in different cell types.

Hyperkyphosis is not dependent on bone mass and quality in the mouse model of Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant disease affecting cardiovascular, ocular and skeletal systems. It is caused by mutations in the fibrillin-1 (FBN1) gene, leading to structural defects of connective tissue and increased activation of TGF-ß. Angiotensin II (ang-II) is involved in TGF-ß activity and in bone mass regulation. Inhibition of TGF-ß signaling by blockage of the ang-II receptor 1 (AT1R) via losartan administration leads to improvement of cardiovascular and pulmonary phenotypes, but has no effect on skeletal phenotype in the haploinsufficient mouse model of MFS mgR, suggesting a distinct mechanism of pathogenesis in the skeletal system. Here we characterized the skeletal phenotypes of the dominant-negative model for MFS mgΔlpn and tested the effect of inhibition of ang-II signaling in improving those phenotypes. As previously shown, heterozygous mice present hyperkyphosis, however we now show that only males also present osteopenia. Inhibition of ang-II production by ramipril minimized the kyphotic deformity, but had no effect on bone microstructure in male mutant animals. Histological analysis revealed increased thickness of the anterior longitudinal ligament (ALL) of the spine in mutant animals (25.8 ± 6.3 vs. 29.7 ± 7.7 µm), coupled with a reduction in type I (164.1 ± 8.7 vs. 139.0 ± 4.4) and increase in type III (86.5 ± 10.2 vs. 140.4 ± 5.6) collagen in the extracellular matrix of this ligament. In addition, we identified in the MFS mice alterations in the erector spinae muscles which presented thinner muscle fibers (1035.0 ± 420.6 vs. 655.6 ± 239.5 µm2) surrounded by increased area of connective tissue (58.17 ± 6.52 vs. 105.0 ± 44.54 µm2). Interestingly, these phenotypes were ameliorated by ramipril treatment. Our results reveal a sex-dependency of bone phenotype in MFS, where females do not present alterations in bone microstructure. More importantly, they indicate that hyperkyphosis is not a result of osteopenia in the MFS mouse model, and suggest that incompetent spine ligaments and muscles are responsible for the development of that phenotype.

Generation of two human induced pluripotent stem cell (hiPSC) lines derived from unrelated Marfan Syndrome patients.

Marfan Syndrome (MFS) is a pleiotropic and autosomal dominant condition caused by pathogenic variants in FBN1. Although fully penetrant, clinical variability is frequently observed among patients and there are only few genotype-phenotype correlations described so far. Here, we describe the generation and characterization of hiPSC lines derived from two unrelated MFS patients harboring heterozygous variants in FBN1. Human iPSCs were obtained from erythroblasts reprogrammed with episomal vectors carrying the reprogramming factors OCT4, SOX2, KLF4, c-MYC and LIN-28, and characterized according to established criteria. Differentiated cells demonstrated different patterns of fibrillin-1 expression suggesting different molecular mechanisms between the two patients.

The mgΔlpn mouse model for Marfan syndrome recapitulates the ocular phenotypes of the disease.

PURPOSE: Fibrillin-1 and -2 are major components of tissue microfibrils that compose the ciliary zonule and cornea. While mutations in human fibrillin-1 lead to ectopia lentis, a major manifestation of Marfan syndrome (MFS), in mice fibrillin-2 can compensate for reduced/lack of fibrillin-1 and maintain the integrity of ocular structures. Here we examine the consequences of a heterozygous dominant-negative mutation in the Fbn1 gene in the ocular system of the mgΔlpn mouse model for MFS. METHODS: Eyes from mgΔlpn and wild-type mice at 3 and 6 months of age were analyzed by histology. The ciliary zonule was analyzed by scanning electron microscopy (SEM) and immunofluorescence. RESULTS: Mutant mice presented a significantly larger distance of the ciliary body to the lens at 3 and 6 months of age when compared to wild-type, and ectopia lentis. Immunofluorescence and SEM corroborated those findings in MFS mice, revealing a disorganized mesh of microfibrils on the floor of the ciliary body. Moreover, mutant mice also had a larger volume of the anterior chamber, possibly due to excess aqueous humor. Finally, losartan treatment had limited efficacy in improving ocular phenotypes. CONCLUSIONS: In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔlpn mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease.

[Mutation c.3037G>A in the FBN1 gene associated with neonatal Marfan syndrome variant]. / Mutación c.3037G>A en el gen FBN1 asociado a síndrome de Marfan variante neonatal.

Marfan syndrome ([MS], OMIM 154700) is a connective tissue disorder that exhibits an autosomal dominant pattern of inheritance, whose clinical characteristics can affect multiple systems or organs in a variable way. It is caused by mutations in the FBN1 gene (OMIM 134797) located at 15q21.1. Neonatal MS is an uncommon variety of the entity associated with missense mutation between exons 23-33 and truncating mutations, exhibits a more severe phenotype and high percentage of mortality in the first years of life. The case of male adolescent with neonatal MS and missense mutation (c.3037G> A; p.Gly225Arg) in exon 24 of the FBN1 gene is presented. Given these findings, interfamilial phenotype variation, the early interdisciplinary medical evaluation necessary for the management of possible complications, as well as the appropriate family genetic counseling were studied.

El síndrome de Marfan ([SM], OMIM 154700) es un trastorno del tejido conectivo que exhibe un patrón de herencia autosómico dominante, cuyas características clínicas pueden afectar de forma variable múltiples sistemas u órganos. Es causado por mutaciones en el gen FBN1 (OMIM 134797) localizado en 15q21.1. El SM neonatal es una variedad infrecuente de la entidad asociado con mutaciones en el cambio de sentido entre los exones 23-33 y mutaciones truncadas, exhibe un fenotipo más severo y alto porcentaje de mortalidad en los primeros años de vida. Se presenta el caso de adolescente masculino con SM neonatal y mutaciones en el cambio de sentido (c.3037G>A; p.Gly225Arg) en el exón 24 del gen FBN1. Ante estos hallazgos se estudió la variación fenotípica interfamiliar, la evaluación médica interdisciplinaria precoz necesaria para el manejo de las posibles complicaciones, así como el oportuno asesoramiento genético familiar.

A positively selected FBN1 missense variant reduces height in Peruvian individuals.

On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.

Is HSPG2 a modifier gene for Marfan syndrome?

Marfan syndrome (MFS) is a connective tissue disease caused by variants in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mg∆loxPneo mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here, we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mg∆loxPneo mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients.

Comparison of Evolution of Aortic Root Dilation and Ghent Criteria in Preadolescents and Adolescents with and without Marfan Syndrome.

OBJECTIVE: To determine whether the Ghent Criteria (2010) can be reliably used in evaluating preadolescents and adolescents for Marfan syndrome by comparing aortic growth, systemic scores, and anthropometric features in individuals with and without Marfan syndrome. STUDY DESIGN: A retrospective chart review was completed for patients less than 15 years of age referred for Marfan syndrome. Comparisons were made between the first and last visit. Paired t tests were used to compare Ghent systemic scores. Wilcoxon rank-sum test were used to compare age, aortic root z scores, height z scores, and body mass index z scores. Recursive partitioning was used to identify combinations of factors to distinguish Marfan syndrome. RESULTS: In total, 53 individuals met inclusion criteria (29 Marfan syndrome and 24 non-Marfan syndrome). Ghent systemic score increased in the Marfan syndrome group and declined in the non-Marfan syndrome. The non-Marfan syndrome group did not develop progressive aortic root dilation with age. Individuals with Marfan syndrome had higher median height z scores than non-Marfan syndrome, with no difference in median body mass index z score between groups. A combination of aortic root z score above 0.95 and Ghent systemic score above 3 was highly indicative of a Marfan syndrome diagnosis in children less than 15 years of age. CONCLUSION: The Ghent criteria (2010) can be used to reliably exclude a diagnosis of Marfan syndrome in individuals less than 15 years of age. Genetic testing should be used as an aide in confirming or excluding the diagnosis of Marfan syndrome in individuals with an aortic root z score above 0.95 in combination with a Ghent systemic score above 3 at initial visit.

Impaired vascular smooth muscle cell force-generating capacity and phenotypic deregulation in Marfan Syndrome mice.

Mechanisms whereby fibrillin-1 mutations determine thoracic aorta aneurysms/dissections (TAAD) in Marfan Syndrome (MFS) are unclear. Most aortic aneurysms evolve from mechanosignaling deregulation, converging to impaired vascular smooth muscle cell (VSMC) force-generating capacity accompanied by synthetic phenotype switch. However, little is known on VSMC mechanoresponses in MFS pathophysiology. Here, we investigated traction force-generating capacity in aortic VSMC cultured from 3-month old mg∆lpn MFS mice, together with morpho-functional and proteomic data. Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression. In parallel, the increased cell area and its complex non-fusiform shape suggested possible transition towards a mesenchymal-like phenotype, confirmed through several markers (e.g. N-cadherin, Slug). MFS-VSMC proteomic profile diverged from that of WT-VSMC particularly regarding lower expression of actin cytoskeleton-regulatory proteins. Accordingly, MFS-VSMC displayed lower traction force-generating capacity and impaired contractile moment at physiological substrate stiffness, and markedly attenuated traction force responses to enhanced substrate rigidity. Such impaired mechanoresponses correlated with decreased number, altered morphology and delocalization of focal adhesions, as well as disorganized actin stress fiber network vs. WT-VSMC. In VSMC cultured from 6-month-old mice, phenotype changes were attenuated and both WT-VSMC and MFS-VSMC generated less traction force, presumably involving VSMC aging, but without evident senescence. In summary, MFS-VSMC display impaired force-generating capacity accompanying a mesenchymal-like phenotype switch connected to impaired cytoskeleton/focal adhesion organization. Thus, MFS-associated TAAD involves mechanoresponse impairment common to other TAAD types, but through distinct mechanisms.

Genome Sequencing Identifies the Pathogenic Variant Missed by Prior Testing in an Infant with Marfan Syndrome.

We describe an infant with a phenotype typical of early onset Marfan syndrome whose genetic evaluation, including Sanger sequencing and deletion/duplication testing of FBN1 and exome sequencing, was negative. Ultimately, genome sequencing revealed a deletion missed on prior testing, demonstrating the unique utility of genome sequencing for molecular genetic diagnosis.

A c.3037G>A mutation in FBN1 gene causing Marfan syndrome with an atypically severe phenotype / Mutación c.3037G>A en el gen FBN1 causa sindrome de Marfan con fenotipo atípico severo

Marfan syndrome is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, mostly caused by mutations in the FBN1 gene, which is located on chromosome 15q21.1 and encoding fibrillin 1. We report a case of Marfan syndrome presen ting with severe ocular and systemic manifestations, such as cardiac congenital anomalies. The patient underwent a multidisciplinary approach and his clinical diagnosis was associated with a c.3037G>A mutation in the FBN1 gene. Identification of this genetic alteration should instigate a prompt multidisciplinary assessment and monitoring, in order to prevent devasta ting consequences such as cardiac and ocular phenotype. Molecular modeling of the mutation highlighted the importance of the preservation of the calcium-dependent structure of an epidermal-growth-factor-like domain of fibrillin-1 and consequently the microfibrillar formation process. This report aims to highlight the importance of an early clinical and molecular diagnosis and once more, the importance of the multidisciplinary approach of this genetic entity.

El síndrome de Marfan es una enfermedad pleitrópica del tejido conjuntivo que exhibe un patrón de herencia autosómico dominante, en su mayoría causado por mutacio nes en el gen FBN1 , que se encuentra en el cromosoma 15q21.1 y codifica a la fibrilina 1. Se presenta un caso de síndrome de Marfan que cursa con manifestación sistémica severa cardíaca y principlamente ocular. El paciente presentó una valoración multidisciplinaria y su diagnóstico clínico fue asociado con la mutación c.3037G>A en el gen FBN1 . La identificación de esta alteración genética debe promover una pronta evaluación y supervisión con el fin de evitar las desvastadoras consecuencias, tales como el fenotipo cardíaco y ocular. El modelado comparativo de proteínas resalta la importancia de la conservación de la estructura del dominio de la fibrilina-1 dependiente de calcio similar al factor de crecimiento epidérmico y por lo tanto el proceso de formación microfibrilar. Este informe tiene como objetivo resaltar la importancia de un diagnóstico clínico y molecular temprano y el enfoque multidisciplinariode esta entidad genética.