Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria.

Autor: Ravenscroft G; Centre for Medical Research, The University of Western Australia and Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia. Electronic address: gina.ravenscroft@perkins.uwa.edu.au., Di Donato N; Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany., Hahn G; Institut und Poliklinik für Radiologische Diagnostik, Universitätsklinikum Dresden, Dresden, Germany., Davis MR; Department of Diagnostic Genomics, Pathwest, Nedlands, Western Australia, Australia., Craven PD; John Hunter Children's Hospital, Hunter Valley, New South Wales, Australia., Poke G; Genetic Health Services, Auckland, New Zealand., Neas KR; Genetic Health Services, Auckland, New Zealand., Neuhann TM; Medizinisch Genetisches Zentrum, Munich, Germany., Dobyns WB; Seattle Children's Research Institute, Seattle, WA, USA., Laing NG; Centre for Medical Research, The University of Western Australia and Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia; Department of Diagnostic Genomics, Pathwest, Nedlands, Western Australia, Australia.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2016 Nov; Vol. 26 (11), pp. 744-748. Date of Electronic Publication: 2016 Sep 19.
DOI: 10.1016/j.nmd.2016.09.009
Abstrakt: Autosomal dominantly inherited mutations of BICD2 are associated with congenital-onset spinal muscular atrophy characterised by lower limb predominance. A few cases have also showed upper motor neuron pathology, including presenting with features resembling hereditary spastic paraplegia. The age-of-onset for the published families is usually at birth but also included cases with childhood- and adult-onset disease. In this report we described two isolated probands that presented in utero with features associated with reduced fetal movements. Both cases were diagnosed at birth with arthrogryposis multiplex congenita (AMC) and hypotonia. Other variable features included congenital fractures, hip dislocation, micrognathia, respiratory insufficiency, microcephaly and bilateral perisylvian polymicrogyria. Patient 1 is 4 years of age and stable, but shows significant motor developmental delay and delayed speech. Patient 2 passed away at 7 weeks of age. Through next generation sequencing we identified the same missense substitution in BICD2 (p.Arg694Cys) in both probands. Sanger sequencing showed that in both cases the mutation arose de novo. The in utero onset in both cases suggests that the p.Arg694Cys substitution may have a more deleterious effect on BICD2 function than previously described mutations. Our results broaden the phenotypes associated with BICD2 mutations to include AMC and cortical malformations and therefore to a similar phenotypic spectrum to that associated with its binding partner DYNC1H1.
(Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: