An Activin Receptor IA/Activin-Like Kinase-2 (R206H) Mutation in Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an exceptionally rare genetic disease that is characterised by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomical areas. This disease is caused by a mutation in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2). A Mexican family with one member affected by FOP was studied. The patient is a 19-year-old female who first presented with symptoms of FOP at 8 years old; she developed spontaneous and painful swelling of the right scapular area accompanied by functional limitation of movement. Mutation analysis was performed in which genomic DNA as PCR amplified using primers flanking exons 4 and 6, and PCR products were digested with Cac8I and HphI restriction enzymes. The most informative results were obtained with the exon 4 flanking primers and the Cac8I restriction enzyme, which generated a 253 bp product that carries the ACVR1 617G>A mutation, which causes an amino acid substitution of histidine for arginine at position 206 of the glycine-serine (GS) domain, and its mutation results in the dysregulation of bone morphogenetic protein (BMP) signalling that causes FOP.

Análise antropofisiológica em paciente com Fibrodisplasia Ossificante Progressiva: casuística / Anthrophophysiological analysis in a patient with Progressive Ossificant Fibrodysplasia: casuistic

“…De acordo com diversos investigadores HERRERA-ESPARZA, et al, 2013;HASAN, 2012;GOSAI, et al, 2013), conclui-se que esta voluntária apresenta um distúrbio respiratório restritivo moderado ocasionado pela diminuição do espaço intratorácico, em virtude da acentuada escoliose torácica de convexidade direcionada à esquerda e de calcificação de tecidos naquela região.…”

“…Maioria dos casos é ocasionada por mutação espontânea nos gametas no gene ACVR1, responsável pela doença. O ACVR1 codifica o receptor activin tipo-1, tipo de receptor BMP (bone morphogenetic protein) tipo-1 e mutação muda o códon 206 de arginina para histadina, ocasionado transformações de células endoteliais em células tronco mesenquimatosas e em osso HERRERA-ESPARZA, et al, 2013). A síndrome designada, em 1868, como miosite ossificante progressiva alterou para fibrosite e, em 1972, para fibrodisplasia (KAPLAN, 2005).…”

DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway

“…Research has reported that ALK2 is generally expressed in various types of cells (12). ALK2 gene mutation was found to lead to ossificans progressiva fibrodysplasia (FOP) in bone disease (13), and led to Down's syndrome. The reason for congenital heart defects in Down's syndrome patients is due to ALK2 gene mutation which alters the BMP/SMAD pathway (14).…”

Classical and Atypical Fibrodysplasia Ossificans Progressiva in India

“…Korea, France, Italy, Brazil, Spain, South, Africa, India, Mexico, Egypt, Turkish, China, Germany (Lin et al, 2006), (Nakajima et al, 2007), , (Lucotte et al, 2008), (Bocciardi et al, 2009), (Carvalho et al, 2010), (Morales-Piga et al, 2012), (Dandara et al, 2012), (Shukla et al, 2013), (Herrera-Esparza et al, 2013), (Al-Haggar et al, 2013), (Eresen Yazıcıoglu et al, 2013), (Zhang et al, 2013), (Stefanova et al, 2012) (Connor & Evans, 1982), (Stefanova et al, 2012), (Carvalho et al, 2010) Exons 8 and 9 c.1067 G>A p.Gly356Asp Present Japan, Germany, China (Kaplan et al, 2009), 3 (Furuya et al, 2008), (Stefanova et al, 2012), (Zhang et al, 2013) Exon 9 c.1124 G>C p.Arg375Pro Absent Unspecified (Kaplan et al, 2009) …”