Universität zu Köln

Haliloglu, Goknur, Becker, Kerstin, Temucin, Cagri, Talim, Beril, Kucuksahin, Nalan, Pergande, Matthias, Motameny, Susanne, Nurnberg, Peter, Aydingoz, Ustun ORCID: 0000-0002-4325-847X, Topaloglu, Haluk and Cirak, Sebahattin (2017). Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects. J. Hum. Genet., 62 (4). S. 497 - 502. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1435-232X

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Abstract

The genetic work-up of arthrogryposis is challenging due to the diverse clinical and molecular etiologies. We report a-18(3/12)-year-old boy, from a 2nd degree consanguineous family, who presented at 3(6/12) years 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Haliloglu, Goknur UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Temucin, Cagri UNSPECIFIED UNSPECIFIED UNSPECIFIED Talim, Beril UNSPECIFIED UNSPECIFIED UNSPECIFIED Kucuksahin, Nalan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pergande, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Motameny, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Aydingoz, Ustun UNSPECIFIED orcid.org/0000-0002-4325-847X UNSPECIFIED Topaloglu, Haluk UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-235612
DOI:	10.1038/jhg.2016.153
Journal or Publication Title:	J. Hum. Genet.
Volume:	62
Number:	4
Page Range:	S. 497 - 502
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1435-232X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DIAGNOSTIC-APPROACH; CHANNELS; CLASSIFICATION; ETIOLOGY; GENETICS Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23561