PT - JOURNAL ARTICLE AU - J Vogt AU - N V Morgan AU - T Marton AU - S Maxwell AU - B J Harrison AU - D Beeson AU - E R Maher TI - Germline mutation in <em>DOK7</em> associated with fetal akinesia deformation sequence AID - 10.1136/jmg.2008.065425 DP - 2009 May 01 TA - Journal of Medical Genetics PG - 338--340 VI - 46 IP - 5 4099 - http://jmg.bmj.com/content/46/5/338.short 4100 - http://jmg.bmj.com/content/46/5/338.full SO - J Med Genet2009 May 01; 46 AB - Background: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor γ subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype.Methods: We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7.Results: A homozygous DOK7 splice site mutation, c.331+1G&gt;T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic “limb girdle” pattern of muscle weakness.Conclusion: This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype.