Affiliations: [a] Dr. John T. Macdonald Foundation, Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA
| [b] Children’s Hospital of Eastern Ontario Research Institute; Division of Neurology, Department of Medicine, The Ottawa Hospital; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada
| [c] Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| [d] Department of Neurology, Medical Faculty, RWTH Aachen University, Aachen, Germany
Correspondence:
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Correspondence to: Stephan Züchner, University of Miami Leonard M. Miller School of Medicine, 1501 NW 10th Avenue, BRB 616 (M-860), Miami, Florida 33136, USA. Tel.: +1 305 243 2281 (Office); Fax: +1 305 243 2703; E-mail: [email protected] and Atchayaram Nalini, Department of Neurology Neuroscience Faculty Block NIMHANS, Bangalore-29, India. Tel.: +91 80 26995139; Fax: +91 80 26564830; E-mail: [email protected].
Abstract: Mutations in PLEKHG5, a pleckstrin homology domain containing member of the GEF family, are associated with distal spinal muscular atrophy and intermediate Charcot-Marie-Tooth disease. Here, we describe an isolated case with distal intermediate neuropathy with scapular winging. By whole exome sequencing, we identified the homozygous PLEKHG5 Arg97Gln missense mutation, located in the N-terminal region of the protein. This mutation resides between a zinc-finger motif and a RBD domain, involved in binding rnd3, a RhoA effector protein. We conclude that based on the characteristic phenotype presented by the patient and the supportive genetic findings, the PLEKHG5 mutation is the causative variant.
