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Sequence variants in muscle tissue‐related genes may determine the severity of muscle contractures in cerebral palsy
Author(s) -
Pingel Jessica,
Andersen Jeppe Dyrberg,
Christiansen Sofie Lindgren,
Børsting Claus,
Morling Niels,
Lorentzen Jakob,
Kirk Henrik,
Doessing Simon,
Wong Christian,
Nielsen Jens Bo
Publication year - 2019
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32693
Subject(s) - gross motor function classification system , cerebral palsy , medicine , physical therapy
Muscle contractures are a common complication to cerebral palsy (CP). The purpose of this study was to evaluate whether individuals with CP carry specific gene variants of important structural genes that might explain the severity of muscle contractures. Next‐generation‐sequencing (NGS) of 96 candidate genes associated with muscle structure and metabolism were analyzed in 43 individuals with CP (Gross Motor Function classification system [GMFCS] I, n =10; GMFCS II, n =14; GMFCS III, n =19) and four control participants. In silico analysis of the identified variants was performed. The variants were classified into four categories ranging from likely benign (VUS0) to highly likely functional effect (VUS3). All individuals with CP were classified and grouped according to their GMFCS level: Statistical comparisons were made between GMFCS groups. Kruskal‐Wallis tests showed significantly more VUS2 variants in the genes COL4 (GMFCS I–III; 1, 1, 5, respectively [ p < .04]), COL5 (GMFCS I–III; 1, 1, 5 [ p < .04]), COL6 (GMFCS I–III; 0, 4, 7 [ p < .003]), and COL9 (GMFCS I–III; 1, 1, 5 [ p < .04]), in individuals with CP within GMFCS Level III when compared to the other GMFCS levels. Furthermore, significantly more VUS3 variants in COL6 (GMFCS I–III; 0, 5, 2 [ p < .01]) and COL7 (GMFCS I–III; 0, 3, 0 [ p < .04]) were identified in the GMFCS II level when compared to the other GMFCS levels. The present results highlight several candidate gene variants in different collagen types with likely functional effects in individuals with CP.