title: Lethal multiple pterygium syndrome, the extreme end of the RYR1 spectrum.
abstract: BACKGROUND
  Lethal multiple pterygium syndrome (LMPS, OMIM 253290), is a fatal disorder associated with anomalies of the skin, muscles and skeleton. It is characterised by prenatal growth failure with pterygium present in multiple areas and akinesia, leading to muscle weakness and severe arthrogryposis. Foetal hydrops with cystic hygroma develops in affected foetuses with LMPS. This study aimed to uncover the aetiology of LMPS in a family with two affected foetuses.
  
  
  RESULTS
  Whole exome sequencing studies have identified novel compound heterozygous mutations in RYR1 in two affected foetuses with pterygium, severe arthrogryposis and foetal hydrops with cystic hygroma, characteristic features compatible with LMPS. The result was confirmed by Sanger sequencing and restriction fragment length polymorphism analysis.
  
  
  CONCLUSIONS
  RYR1 encodes the skeletal muscle isoform ryanodine receptor 1, an intracellular calcium channel with a central role in muscle contraction. Mutations in RYR1 have been associated with congenital myopathies, which form a continuous spectrum of pathological features including a severe variant with onset in utero with fetal akinesia and arthrogryposis. Here, the results indicate that LMPS can be considered as the extreme end of the RYR1-related neonatal myopathy spectrum. This further supports the concept that LMPS is a severe disorder associated with defects in the process known as excitation-contraction coupling.
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Siavash
authors.initials: S
authors.lastname: Ghaderi-Sohi
authors.affiliation: Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Hossein-Nejad Nedai
authors.affiliation: Division of Thoracic Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Varasteh
authors.affiliation: Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden.
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Moslemi
authors.affiliation: Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden. homa.tajsharghi@gu.se.|Department of Clinical and Medical Genetics, University of Gothenburg, SE-405 30, Gothenburg, Sweden. homa.tajsharghi@gu.se.|Systems Biology Research Centre, School of Biomedicine, University of Skövde, SE-541 28, Skövde, Sweden. homa.tajsharghi@gu.se.
authors.forename: Homa
authors.initials: H
authors.lastname: Tajsharghi
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005313:Fetal Death; D005333:Fetus / Q000473:pathology; D006801:Humans; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012868:Skin Abnormalities / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel