title: Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects.
abstract: The genetic work-up of arthrogryposis is challenging due to the diverse clinical and molecular etiologies. We report a-183/12-year-old boy, from a 2nd degree consanguineous family, who presented at 36/12years with hypotonia, distal laxity, contractures, feeding difficulties at birth. He required surgery for progressive scoliosis at 16 years of age, and walked independently since then with an unstable gait and coordination defects. His latest examination at 18 years of age revealed a proprioceptive defect and loss-of-joint position sense in the upper limbs. Somatosensory evoked potentials supported bilateral involvement of dorsal column-medial lemniscal sensory pathways and nerve conduction studies revealed a mild axonal neuropathy. Muscle biopsy showed myopathic changes with neonatal myosin expression. Mendeliome sequencing led to the discovery of a recessive stop mutation in piezo-type mechanosensitive ion channel component 2 (PIEZO2, NM_022068, c.1384C>T, p.R462*). PIEZO2 is a nonselective cation channel, expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs. Dominant PIEZO2 mutations were described in patients with distal arthrogryposis type 5 and Marden-Walker syndrome. Sensory ataxia and proprioception defect with dorsal column involvement together with arthrogryposis, myopathy, scoliosis and progressive respiratory failure may represent a distinct clinical phenotype, and indicate recessive mutations in PIEZO2.
authors.affiliation: Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.
authors.forename: Goknur
authors.initials: G
authors.lastname: Haliloglu
authors.affiliation: Department of Pediatrics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Neurology, Hacettepe University, Ankara, Turkey.
authors.forename: Cagri
authors.initials: C
authors.lastname: Temucin
authors.affiliation: Pediatric Pathology Unit, Department of Pediatrics, Hacettepe University, Ankara, Turkey.
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.affiliation: Department of Neurology, Hacettepe University, Ankara, Turkey.
authors.forename: Nalan
authors.initials: N
authors.lastname: Küçükşahin
authors.affiliation: Department of Pediatrics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pergande
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Motameny
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Department of Radiology, Hacettepe University, Ankara, Turkey.
authors.forename: Ustun
authors.initials: U
authors.lastname: Aydingoz
authors.affiliation: Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.affiliation: Department of Pediatrics, University Hospital Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
mesh_terms: D000293:Adolescent; D001176:Arthrogryposis / Q000235:genetics* / Q000503:physiopathology; D005073:Evoked Potentials, Somatosensory; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D012600:Scoliosis / Q000235:genetics* / Q000503:physiopathology; D020886:Somatosensory Disorders / Q000235:genetics* / Q000503:physiopathology
chemical_list: D007473:Ion Channels; C000589132:PIEZO2 protein, human