Biallelic intragenic deletion in  MASP1  in an adult female with 3MC syndrome

Graul‐Neumann, Luitgard; Mensah, Martin A.; Klopocki, Eva; Uebe, Steffen; Ekici, Arif B.; Thiel, Christian T.; Reis, André; Zweier, Christiane

doi:10.1016/j.ejmg.2018.01.016

Cited by 17 publications

(14 citation statements)

References 17 publications

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“…In 2017, Munye et al [9] reported 3 patients with COLEC11, 1 patient with MASP1 and 3 patients with COLEC10 mutation. Therefore, in total, together with the isolated cases recently reported, 43 3MC patients with mutations in COLEC11, MASP1 or COLEC10 have been identified until now [17,18]. Among 43 patients, 23 patients had mutations in MASP1 gene [9,10,13].…”

Section: Discussionmentioning

confidence: 90%

3MC sendromu: Bir olgu sunumu

Çakmaklı¹,

Kandur²

2019

Archives of Clinical and Experimental Medicine

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3MC syndrome is a rare autosomal recessive disorder associated with distinctive facial features, cleft lip/palate, short stature, developmental delay, periumbilical defects, genitourinary and sacral anomalies. Mutations in the genes which encode proteins involved in the lectin complement pathway of innate immune system; MASP1, COLEC11 and COLEC10 have been identified in patients with 3MC syndrome. We report a 2-year-old male patient with 3MC syndrome; in whom diagnosis was confirmed by mutation analysis of the MASP1 gene.

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Section: Discussionmentioning

confidence: 90%

3MC sendromu: Bir olgu sunumu

Çakmaklı¹,

Kandur²

2019

Archives of Clinical and Experimental Medicine

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“…However, it appears not to be indispensable since deficiencies are observed in healthy individuals and blood donors (García-Laorden et al, 2020). Mutations in the MASP1 gene have also been reported in families with 3MC syndrome (Sirmaci et al, 2010;Graul-Neumann et al, 2018;Basdemirci et al, 2019). The large majority of MASP genetic variants are located in exons coding for the specific serine protease domain of MASP-3 (Gajek et al, 2020).…”

Section: The Components Of the Lectin Pathway Theirmentioning

confidence: 99%

Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics

2021

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The complement system was discovered at the end of the 19th century as a heat-labile plasma component that “complemented” the antibodies in killing microbes, hence the name “complement.” Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. Significance Statement The complement system is the host’s defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host’s enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.

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“…Several different potentially deleterious mutations in genes of the lectin arm of the complement system -such as MASP1, COLEC10, and COLEC11 genes -have been described in patients with 3MC syndrome (Sirmaci et al, 2010;Rooryck et al, 2011;Atik et al, 2015;Urquhart et al, 2016;Gardner et al, 2017;Munye et al, 2017;Graul-Neumann et al, 2018;Basdemirci et al, 2019). It has recently been shown that disease-associated mutations in COLEC10 and COLEC11 inhibit either production or secretion of encoded proteins in mammalian cells (Rooryck et al, 2011;Venkatraman Girija et al, 2015), which may explain the undetectable levels of CL-K1 in the serum of affected individuals (Rooryck et al, 2011).…”

Section: Complement In 3mc Syndromementioning

confidence: 99%

Complement System in Brain Architecture and Neurodevelopmental Disorders

et al. 2020

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Current evidence indicates that certain immune molecules such as components of the complement system are directly involved in neurobiological processes related to brain development, including neurogenesis, neuronal migration, synaptic remodeling, and response to prenatal or early postnatal brain insults. Consequently, complement system dysfunction has been increasingly implicated in disorders of neurodevelopmental origin, such as schizophrenia, autism spectrum disorder (ASD) and Rett syndrome. However, the mechanistic evidence for a causal relationship between impaired complement regulation and these disorders varies depending on the disease involved. Also, it is still unclear to what extent altered complement expression plays a role in these disorders through inflammation-independent or-dependent mechanisms. Furthermore, pathogenic mutations in specific complement components have been implicated in the etiology of 3MC syndrome, a rare autosomal recessive developmental disorder. The aims of this review are to discuss the current knowledge on the roles of the complement system in sculpting brain architecture and function during normal development as well as after specific inflammatory insults, such as maternal immune activation (MIA) during pregnancy, and to evaluate the existing evidence associating aberrant complement with developmental brain disorders.

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Biallelic intragenic deletion in MASP1 in an adult female with 3MC syndrome

Cited by 17 publications

References 17 publications

3MC sendromu: Bir olgu sunumu

3MC sendromu: Bir olgu sunumu

Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics

Complement System in Brain Architecture and Neurodevelopmental Disorders

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