Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures.
Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposis. Some observations suggest that these dominant mutations induce a gain-of-function effect on the channel. Here, we report a consanguineous family with three siblings who showed short stature, scoliosis, gross motor impairment, and a progressive form of contractures involving the distal joints that is distinct from that found in patients with dominant mutations in PIEZO2. These siblings also displayed deficits in proprioception and touch sensation. Whole-exome sequencing performed in the three affected siblings revealed the presence of a rare homozygous variant (c.2708C>G; p.S903*) in PIEZO2. This variant is predicted to disrupt PIEZO2 function by abolishing the pore domain. Sanger sequencing confirmed that all three siblings are homozygous whereas their parents and an unaffected sibling are heterozygous for this variant. Recessive mutations in PIEZO2 thus appear to cause a progressive phenotype that overlaps with, while being mostly distinct from that associated with dominant mutations in the same gene.
CHU Sainte-Justine Research Center, Montreal, Canada.
A A
AA
Mahmud
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
N A
NA
Nahid
CHU Sainte-Justine Research Center, Montreal, Canada.
C
C
Nassif
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
M S B
MS
Sayeed
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
M U
MU
Ahmed
Department of Pediatric Neuroscience, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh.
M
M
Parveen
Department of Neurology, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh.
M I
MI
Khalil
Department of Physiotherapy, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh.
M M
MM
Islam
Department of Pharmacy, Northern University Bangladesh, Dhaka, Bangladesh.
Z
Z
Nahar
Department of Medical Imaging, CHU Sainte-Justine, Montreal, Québec, Canada.
F
F
Rypens
CHU Sainte-Justine Research Center, Montreal, Canada.
F F
FF
Hamdan
Montreal Neurological Institute, McGill University, Montreal, Québec, Canada.
G A
GA
Rouleau
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
A
A
Hasnat
CHU Sainte-Justine Research Center, Montreal, Canada.|Department of Pediatrics, Université de Montréal, Montreal, Canada.|Department of Neurosciences, Université de Montréal, Montreal, Canada.
J L
JL
Michaud
D000328:Adult; D001176:Arthrogryposis / Q000235:genetics* / Q000503:physiopathology; D001459:Bangladesh; D003241:Consanguinity; D003286:Contracture / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D011434:Proprioception / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics / Q000503:physiopathology; D035781:Siblings; D014110:Touch / Q000235:genetics
D007473:Ion Channels; C000589132:PIEZO2 protein, human
PIEZO2; arthrogryposis; mechanotransduction; proprioception