RT Journal Article SR Electronic T1 Germline mutation in DOK7 associated with fetal akinesia deformation sequence JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 338 OP 340 DO 10.1136/jmg.2008.065425 VO 46 IS 5 A1 Vogt, J A1 Morgan, N V A1 Marton, T A1 Maxwell, S A1 Harrison, B J A1 Beeson, D A1 Maher, E R YR 2009 UL http://jmg.bmj.com/content/46/5/338.abstract 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>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.