Rare copy number variants in the genome of Chinese female children and adolescents with Turner syndrome

Abstract

Turner syndrome (TS) is a congenital disease caused by complete or partial loss of one X chromosome. Low bone mineral status is a major phenotypic characteristic of TS that can not be fully explained by X chromosome loss, suggesting other autosomal-linked mutations may also exist. Therefore, the present study aimed to detect potential genetic mutations in TS through examination of copy number variation (CNV). Seventeen patients with TS and 15 healthy volunteer girls were recruited. Array-based comparative genomic hybridization (a-CGH) was performed on whole blood genomic DNA (gDMA) from the 17 TS patients and 15 healthy volunteer girls to identify potential CNVs. The abnormal CNV of one identified gene (CARD11) was verified by quantitative PCR. All cases diagnosed had TS based on genotype examination and physical characteristics, including short stature and premature ovarian failure. Three rare CNVs, located individually at 7p22.3, 7p22.2, and Xp22.33, where six genes (TTYH3, AMZ1, GNA12, BC038729, CARD11, and SHOX (stature homeobox)) are located, were found in TS patients. Quantitative PCR confirmed the CNV of CARD11 in the genome of TS patients. Our results indicate that CARD11 gene is one of the mutated genes involved in TS disease. However, this CNV is rare and its contribution to TS phenotype requires further study.

Human Sex Matters: Y-linked lysine demethylase 5D drives accelerated male osteogenic differentiation

“…Likewise, we detected a male-specific elevated expression of the lncRNA FAM157C, which is commonly known to be expressed in the human bone marrow (33). Li and coworkers showed deletion of FAM157C as one rare copy number variant being present in female patients suffering from turner syndrome (34). Turner syndrome is a congenital disease caused by loss of one X-chromosome, which results amongst other phenotypic characteristics in a severe bone fragility including low bone mineral density and an elevated fracture risk (reviewed in (35)).…”

Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation

“…Likewise, we detected a male-specific elevated expression of the lncRNA FAM157C, which is commonly known to be expressed in the human bone marrow [ 51 ]. Li and coworkers showed deletion of FAM157C as one rare copy number variant being present in female patients suffering from turner syndrome [ 52 ]. Turner syndrome is a congenital disease caused by loss of one X-chromosome, which results, among other phenotypic characteristics, in a severe bone fragility including low bone mineral density and an elevated fracture risk (reviewed in [ 53 ]).…”

Effect of Hormone Replacement Therapy on Bone Mineral Density and Body Composition in Chinese Adolescent and Young Adult Turner Syndrome Patients

“…A total of 20 adolescent and young adult TS patients (including X0 and mosaicism, diagnosed based on the results of chromosome analysis, for details see Supplementary Table 1) with primary amenorrhea participated in the current study. For each subject, cytogenetic analysis was performed on peripheral blood lymphocytes according to standard Giemsa stain G banding technology with 350–450 bands, more than 30 cells were karyotyped per patient (13). Exclusion criteria for our study were other chronic bone diseases which may influence BMD (e.g., osteochondrodysplasia and malignant osteopetrosis), other diseases which may influence BMD (e.g., type 1 or type 2 diabetes, hyperthyroidism, coeliac disease, other thyroid disorders) or treatment with drugs associated with bone metabolism or BMD (e.g., glucocorticoid and growth hormone).…”