Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature.

TitleExome sequencing reveals genetic architecture in patients with isolated or syndromic short stature.
Publication TypeJournal Article
Year of Publication2021
AuthorsFan, X, Zhao, S, Yu, C, Wu, D, Yan, Z, Fan, L, Song, Y, Wang, Y, Li, C, Ming, Y, Gui, B, Niu, Y, Li, X, Yang, X, Luo, S, Zhang, Q, Zhao, X, Pan, H, Li, M, Xia, W, Qiu, G, Liu, P, Zhang, S, Zhang, J, Wu, Z, Lupski, JR, Posey, JE, Chen, S, Gong, C, Wu, N
Corporate AuthorsDeciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study
JournalJ Genet Genomics
Date Published2021 May 20
KeywordsAdolescent, Alleles, Child, Child, Preschool, China, Disease Management, DNA Copy Number Variations, Dwarfism, Exome, Exome Sequencing, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Male, Mutation, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Syndrome

Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations. Although the diagnostic utility of clinical genetic testing in short stature has been implicated, the genetic architecture and the utility of genomic studies such as exome sequencing (ES) in a sizable cohort of patients with short stature have not been investigated systematically. In this study, we recruited 561 individuals with short stature from two centers in China during a 4-year period. We performed ES for all patients and available parents. All patients were retrospectively divided into two groups: an isolated short stature group (group I, n = 257) and an apparently syndromic short stature group (group II, n = 304). Causal variants were identified in 135 of 561 (24.1%) patients. In group I, 29 of 257 (11.3%) of the patients were solved by variants in 24 genes. In group II, 106 of 304 (34.9%) patients were solved by variants in 57 genes. Genes involved in fundamental cellular process played an important role in the genetic architecture of syndromic short stature. Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.

Alternate JournalJ Genet Genomics
PubMed ID34006472
Grant ListUM1 HG006542 / HG / NHGRI NIH HHS / United States
K08 HG008986 / HG / NHGRI NIH HHS / United States

Similar Publications