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PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review
Author(s) -
Yamaguchi Tomomi,
Takano Kyoko,
Inaba Yuji,
Morikawa Manami,
Motobayashi Mitsuo,
Kawamura Rie,
Wakui Keiko,
Nishi Eriko,
Hirabayashi Shinichi,
Fukushima Yoshimitsu,
Kato Hiroyuki,
Takahashi Jun,
Kosho Tomoki
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61142
Subject(s) - arthrogryposis , hypotonia , proprioception , frameshift mutation , neurological examination , medicine , neuroscience , muscle contracture , exome sequencing , anatomy , physical medicine and rehabilitation , psychology , biology , mutation , genetics , gene , pediatrics
PIEZO2 encodes a mechanically activated cation channel, which is abundantly expressed in dorsal root ganglion neuron and sensory endings of proprioceptors required for light touch sensation and proprioception in mice. Biallelic loss‐of‐function mutations in PIEZO2 (i.e., PIEZO2 deficiency) were recently found to cause an arthrogryposis syndrome. Sixteen patients from eight families have been reported to date. Herein we report a new case, including detailed clinical characteristics and courses as well as comprehensive neurological features. The patient was a 12‐year‐old girl presenting with congenital multiple contractures, progressive severe scoliosis, prenatal‐onset growth impairment, motor developmental delay with hypotonia and myopathy‐like muscle pathology, mild facial features, and normal intelligence. Her neurological features included areflexia, impaired proprioception, and decreased senses. Neurophysiological examination revealed decreased amplitude of sensory nerve action potentials, absent H reflex, and prolongation of central conduction times. Clinical exome sequencing revealed a novel homozygous frameshift mutation in PIEZO2 (NM_022068: c.4171_4174delGTCA: p.Val1391Lysfs*39) with no detectable mRNA expression of the gene. PIEZO2 deficiency represents a clinical entity involving characteristic neuromuscular abnormalities and physical features. Next generation sequencing‐based comprehensive molecular screening and extensive neurophysiological examination could be valuable for diagnosis of the disorder.