Context: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach.
Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder.
Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31).
Patients And Methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups.
Main Outcome Measures: Frequencies of pathogenic findings.
Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients.
Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.
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http://dx.doi.org/10.1530/EJE-19-0785 | DOI Listing |
Integr Zool
December 2024
Institute of Eastern-Himalaya Biodiversity Research, Dali University, Dali, Yunnan, China.
Twin Res Hum Genet
December 2024
Independent researchers.
We analyzed whole-genome sequencing (WGS) data from 51 populations and combined WGS and array data from 89 populations. Multiple types of polygenic scores (PGS) were employed, derived from multi-ancestry, between-family genome-wide association study (GWAS; MIX-Height), European-ancestry, between-family GWAS (EUR-Height), and European-ancestry siblings GWAS (SIB-Height). Our findings demonstrate that both genetic and environmental factors significantly influence adult body height between populations.
View Article and Find Full Text PDFSkeletal Radiol
December 2024
Department of Clinical Genomics, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA.
COL9A1 encodes the alpha-1 chain of type IX collagen heterotrimer, which is a vital component of collagen fibrils in hyaline cartilage. There are preliminary lines of evidence suggesting that COL9A1 mutations may be associated with autosomal dominant multiple epiphyseal dysplasia (MED), a disorder affecting the epiphysis of long bones. With only 2 reported cases (both from the same family) of MED in autosomal dominant COL9A1-related disorders (MIM 614135) in the clinical scientific literature hitherto, the phenotype is poorly understood at present.
View Article and Find Full Text PDFBackground: Reduction in adult height by high-dose sex steroids was introduced decades ago. Here, we present the impact of lower doses of sex steroids on the predicted adult height in tall stature.
Methods: This single-center retrospective observational study included 22 tall children treated with low-dose sex steroids.
Background: Primary spontaneous pneumothorax (PSP) has been the subject of many studies, but its pathogenesis remains unclear. Most juvenile PSPs have a tall stature, thin build, and flat thorax, which is described as a "pneumothorax body shape." In this study, we compared the body shapes of spontaneous pneumothorax (SP) patients in their teens and 20s and examined the characteristics of SP patients.
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