TY - JOUR
T1 - Phenotypic variability of TRPV4 related neuropathies
AU - Evangelista, Teresinha
AU - Bansagi, Boglarka
AU - Pyle, Angela
AU - Griffin, Helen
AU - Douroudis, Konstantinos
AU - Polvikoski, Tuomo
AU - Antoniadi, Thalia
AU - Bushby, Kate
AU - Straub, Volker
AU - Chinnery, Patrick F.
AU - Lochmüller, Hanns
AU - Horvath, Rita
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot-Marie-Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina TruseqTM 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies.
AB - Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot-Marie-Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina TruseqTM 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies.
KW - Axonal neuropathy
KW - Congenital distal spinal muscular atrophy
KW - Hereditary motor and sensory neuropathy type 2C
KW - Scapuloperoneal spinal muscular atrophy
KW - Skeletal dysplasia
KW - Transient receptor potential vanilloid 4 gene
UR - http://www.scopus.com/inward/record.url?scp=84929653664&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2015.03.007
DO - 10.1016/j.nmd.2015.03.007
M3 - Article
C2 - 25900305
AN - SCOPUS:84929653664
SN - 0960-8966
VL - 25
SP - 516
EP - 521
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 6
ER -