Loss of the proprioception and touch sensation channel <scp>PIEZO2</scp> in siblings with a progressive form of contractures

Mahmud, Abdullah Al; Nahid, Noor Ahmed; Nassif, Christina; Sayeed, Muhammad Shahdaat Bin; Ahmed, Masud; Parveen, Monowara; Khalil, Mohammad Ibrahim; Islam, M. Saidul; Nahar, Zabun; Rypens, Françoise; Hamdan, Fadi F.; Rouleau, Guy A.; Hasnat, Abul; Michaud, Jacques L.

doi:10.1111/cge.12850

Cited by 66 publications

(44 citation statements)

References 12 publications

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“…Additionally, knockout studies in mice show that Piezo2 is critical for many aspects of light touch and proprioception. In agreement with the mouse data, humans carrying non-functional Piezo2 display profound mechanosensory and proprioceptive deficits (Chesler et al, 2016; Delle Vedove et al, 2016; Mahmud et al, 2016). Knockdown experiments also indicate that it may play a role in the development of hyperalgesia.…”

Section: Discussionsupporting

confidence: 85%

Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebrates

Anderson

Schneider

Bagriantsev

2017

Current Topics in Membranes

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Mechanosensitivity is a fundamental physiological capacity, which pertains to all life forms. Progress has been made with regard to understanding mechanosensitivity in bacteria, flies, and worms. In vertebrates, however, the molecular identity of mechanotransducers in somatic and neuronal cells has only started to appear. The Piezo family of mechanogated ion channels marks a pivotal milestone in understanding mechanosensitivity. Piezo1 and Piezo2 have now been shown to participate in a number of processes, ranging from arterial modeling to sensing muscle stretch. In this review, we focus on Piezo2 and its role in mediating mechanosensation and proprioception in vertebrates.

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Section: Discussionsupporting

confidence: 85%

Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebrates

Anderson

Schneider

Bagriantsev

2017

Current Topics in Membranes

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“…; Mahmud et al. ). In addition to these sensory deficits, mutations in Piezo2 are responsible for complex syndromes that involve joints, ocular muscles and bones (see McMillin et al.…”

Section: Introductionmentioning

confidence: 98%

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity

et al. 2017

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The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch-gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell-neurite complexes, Meissner-like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20 , chromogranin A and synaptophisin ) Merkel cells. Most of them were in close contact with Piezo2 nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2 , but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non-nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans.

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“…The majority of PIEZO2 dominant mutations are clustered in 2 regions of the gene that encode the C-terminal domain and appear to be mutation hotspots, particularly the last exon 52. In contrast, the mutations in recessive DAIPT do not show any locus predilection, as they are distributed throughout the entire gene [Chesler et al, 2016;Delle Vedove et al, 2016;Haliloglu et al, 2017;Mahmud et al, 2017]. The PIEZO2 protein contains more than 30 transmembrane domains and functions as part of mechanically activated cation channels [Coste et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

“…A wide range of sensory and kinematic functions was studied in 2 patients who both carried compound heterozygous mutations in the PIEZO2 gene [Chesler et al, 2016]. Mahmud et al [2017] and Haliloglu et al [2017] reported 4 more patients from 2 families. The heterozygous carriers (parents and siblings) were healthy.…”

mentioning

confidence: 99%

Distal Arthrogryposis with Impaired Proprioception and Touch: Description of an Early Phenotype in a Boy with Compound Heterozygosity of PIEZO2 Mutations and Review of the Literature

Behunova¹,

Bujalkova²,

Gras³

et al. 2018

Mol Syndromol

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The recessive PIEZO2-associated disease, distal arthrogryposis with impaired proprioception and touch (DAIPT), is characterized by hypotonia, perinatal respiratory distress, significantly delayed motor milestones, and progressive symptoms of distal arthrogryposis and scoliosis. Here, we describe the youngest patient with DAIPT to date, who, at the age of 3.5 years, did not show a single clinical sign of distal arthrogryposis or contractures, but had a history of bilateral clubfoot operations. On the contrary, he presented with some features, not described thus far, such as syringohydromyelia, a small cyst of the spinal cord, moderate microcephaly with premature closure of anterior fontanelle, and spontaneous unilateral patella dislocation at the age of 32 months. Using whole exome sequencing, we identified 2 new different loss-of-function mutations in the PIEZO2 gene in our patient. We also review the phenotypes of all 16 previously published patients with DAIPT, summarize the distinctive clinical features of this rare genetic disorder, and recommend that DAIPT be included in the differential diagnosis of floppy infant. PIEZO2 is a unique ion channel that converts mechanical impulses into cellular signals and is involved in various mechanotransduction pathways. In addition to DAIPT, mutations in PIEZO2 have been described to cause 3 more distinct phenotypes of distal arthrogryposis, which are dominant and associated with gain-of-function mutations. On the contrary, recessive DAIPT is associated with loss-of-function PIEZO2 mutations.

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Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures

Cited by 66 publications

References 12 publications

Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebrates

Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebrates

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity

Distal Arthrogryposis with Impaired Proprioception and Touch: Description of an Early Phenotype in a Boy with Compound Heterozygosity of PIEZO2 Mutations and Review of the Literature

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