The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
Depletion of <i>ptk7</i> is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of <i>PTK7</i> has been reported previously in a patient with AIS. In this study, we systemically investig...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | article |
| Language: | EN |
| Published: |
MDPI AG
2021
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| Subjects: | |
| Online Access: | https://doaj.org/article/09d891cf3fac4b77a9a53608bbd62e87 |
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| Summary: | Depletion of <i>ptk7</i> is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of <i>PTK7</i> has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of <i>PTK7</i> in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study. We identified a total of four rare variants in CS and four variants in AIS, including one protein truncating variant (c.464_465delAC) in a patient with CS. We then explored the effects of these variants on protein expression and sub-cellular location. We confirmed that the c.464_465delAC variant causes loss-of-function (LoF) of <i>PTK7</i>. In addition, the c.353C>T and c.2290G>A variants identified in two patients with AIS led to reduced protein expression of PTK7 as compared to that of the wild type. In conclusion, LoF and hypomorphic variants are associated with CS and AIS, respectively. |
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