| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-113 |
Sentence |
denotes |
A Germline Variant in the PANX1 Gene Has Reduced Channel Function and Is Associated with Multisystem Dysfunction. |
| T2 |
114-218 |
Sentence |
denotes |
Pannexin1 (PANX1) is probably best understood as an ATP release channel involved in paracrine signaling. |
| T3 |
219-350 |
Sentence |
denotes |
Given its ubiquitous expression, PANX1 pathogenic variants would be expected to lead to disorders involving multiple organ systems. |
| T4 |
351-537 |
Sentence |
denotes |
Using whole exome sequencing, we discovered the first patient with a homozygous PANX1 variant (c.650G→A) resulting in an arginine to histidine substitution at position 217 (p.Arg217His). |
| T5 |
538-728 |
Sentence |
denotes |
The 17-year-old female has intellectual disability, sensorineural hearing loss requiring bilateral cochlear implants, skeletal defects, including kyphoscoliosis, and primary ovarian failure. |
| T6 |
729-865 |
Sentence |
denotes |
Her consanguineous parents are each heterozygous for this variant but are not affected by the multiorgan syndromes noted in the proband. |
| T7 |
866-1007 |
Sentence |
denotes |
Expression of the p.Arg217His mutant in HeLa, N2A, HEK293T, and Ad293 cells revealed normal PANX1 glycosylation and cell surface trafficking. |
| T8 |
1008-1125 |
Sentence |
denotes |
Dye uptake, ATP release, and electrophysiological measurements revealed p.Arg217His to be a loss-of-function variant. |
| T9 |
1126-1248 |
Sentence |
denotes |
Co-expression of the mutant with wild-type PANX1 suggested the mutant was not dominant-negative to PANX1 channel function. |
| T10 |
1249-1382 |
Sentence |
denotes |
Collectively, we demonstrate a PANX1 missense change associated with human disease in the first report of a "PANX1-related disorder." |
