Abstract
Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition that becomes evident before birth, with pterygium at multiple joints and akinesia. There are two forms of this syndrome that are differentiated by clinical severity: the milder form, Escobar type (OMIM#265000), and the more severe form, lethal type (OMIM#253290). Mutations in CHRNG, which encode the acetylcholine receptor gamma subunit, cause most cases of MPS. Here, we present three patients from two unrelated families showing multiple joint contractures in both the upper and lower limbs. High-arched palates with malocclusion, short neck and micrognathia were observed in all patients. Peripheral blood karyotypes were normal. Whole-exome sequencing analysis of the patients’ genomes led to the discovery of identical missense (p.Pro143Arg) and frameshift deletion variants (p.Pro251fs*45) on CHRNG. These were rare cases of congenital arthrogryposis multiplex related to novel recessive CHRNG variants in two Korean kindred without apparent relatedness.
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References
Karlin, A . Emerging structure of the nicotinic acetylcholine receptors. Nat. Rev. Neurosci. 3, 102–114 (2002).
Morgan, N. V ., Brueton, L. A ., Cox, P ., Greally, M. T ., Tolmie, J . & Pasha, S . et al. Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome. Am. J. Hum. Genet. 79, 390–395 (2006).
Hoffmann, K ., Muller, J. S ., Stricker, S ., Megarbane, A ., Rajab, A . & Lindner, T. H . et al. Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am. J. Hum. Genet. 79, 303–312 (2006).
Vogt, J ., Morgan, N. V ., Rehal, P ., Faivre, L ., Brueton, L. A . & Becker, K . et al. CHRNG genotype-phenotype correlations in the multiple pterygium syndromes. J. Med. Genet. 49, 21–26 (2012).
Choi, M ., Scholl, U. I ., Ji, W ., Liu, T ., Tikhonova, I. R . & Zumbo, P . et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl Acad. Sci. USA 106, 19096–19101 (2009).
Goh, G . & Choi, M . Application of whole exome sequencing to identify disease-causing variants in inherited human diseases. Genomics Inform. 10, 214–219 (2012).
Pollard, K. S ., Hubisz, M. J . & Siepel, A . Detection of non-neutral substitution rates on mammalian phylogenies. Genome Res. 20, 110–121 (2010).
Ng, P. C . & Henikoff, S . SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 31, 3812–3814 (2003).
Adzhubei, I. A ., Schmidt, S ., Peshkin, L ., Ramensky, V. E ., Gerasimova, A . & Bork, P . et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).
Michalk, A ., Stricker, S ., Becker, J ., Rupps, R ., Pantzar, T . & Miertus, J . et al. Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am. J. Hum. Genet. 82, 464–476 (2008).
Koenen, M ., Peter, C ., Villarroel, A ., Witzemann, V . & Sakmann, B . Acetylcholine receptor channel subtype directs the innervation pattern of skeletal muscle. EMBO Rep. 6, 570–576 (2005).
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Seo, J., Choi, IH., Lee, J. et al. Rare cases of congenital arthrogryposis multiplex caused by novel recurrent CHRNG mutations. J Hum Genet 60, 213–215 (2015). https://doi.org/10.1038/jhg.2015.2
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DOI: https://doi.org/10.1038/jhg.2015.2
