Inconsistency of Karyotyping and Array Comparative Genomic Hybridization (aCGH) in a Mosaic Turner Syndrome Case

Abstract

Purpose Turner syndrome is a sex chromosomal aberration where majority of the patients have 45,X karyotype, while several patients are mosaic involving 45,X/46,XX; 46,X,i(Xq); and other variants. Cytogenetic analysis, karyotyping, is considered to be the “gold standard” to detect numerical and structural chromosomal abnormalities. In the recent years, alternative approaches, such as array comparative genomic hybridization (aCGH), have been widely used in genetic analysis to detect numerical abnormalities as well as unbalanced structural rearrangements. In this study, we report the use of karyotyping as well as aCGH in detecting a possible Turner syndrome variant. Methods An apparent 16-year-old female was clinically diagnosed as Turner syndrome with premature ovarian failure and short stature. The genetic diagnosis was performed for the patient and the parents by karyotyping analysis. aCGH was also performed for the patient. Main Findings Cytogenetic analysis of the patient was performed showing variant Turner syndrome (46,X,i(X)(q10)[26]/46,X,del(X)(q11.2)[11]/45,X[8]/46,XX[5]). The patient's aCGH result revealed that she has a deletion of 57,252kb of Xp22.33-p11.21 region; arr[GRCh37] Xp22.33-p11.21 (310,932–57,563–078)X1. Both aCGH and fluorescence in situ hybridization (FISH) results suggested that short stature Homeobox-containing (SHOX) gene, which is located on Xp22.33, was deleted, though FISH result indicated that this was in a mosaic pattern. Conclusion In the recent years, aCGH has become the preferred method in detecting numerical abnormalities and unbalanced chromosomal rearrangements. However, its use is hindered by its failure of detecting mosaicism, especially low-level partial mosaicism. Therefore, although the resolution of the aCGH is higher, the cytogenetic investigation is still the first in line to detect mosaicism.

Evaluation of chromosomal abnormalities in the postnatal cohort: A single‐center study on 14,242 patients

“…However, since array technology is a more sensitive and high‐resolution method, it provides a great advantage in detecting small‐scale genetic changes and performing a more detailed genetic analysis 5 . While array technology offers higher resolution, cytogenetic investigation remains the primary method for detecting mosaicism 6 . Therefore, using both methods together in clinical practice enables genetic diagnosis and counseling processes to be carried out more effectively and comprehensively.…”

“… 5 While array technology offers higher resolution, cytogenetic investigation remains the primary method for detecting mosaicism. 6 Therefore, using both methods together in clinical practice enables genetic diagnosis and counseling processes to be carried out more effectively and comprehensively. The findings suggest that chromosomal analysis should be used in the search for patients with genetic disorders of unknown origin to confirm clinical diagnosis and appropriate medical care after genetic counseling and management.…”

Non-Invasive Screening Test Paradox in a Case Born with Mixed Gonadal Dysgenesis (45,X/46,Xy)

“…Turner syndrome (TS) is a chromosomal disorder commonly observed in females and caused by structural or numerical abnormalities of the X chromosome. TS affects 1 in 2500 live births [ 1 ]. Patients diagnosed with Turner syndrome have a unique phenotype that includes a webbed neck, broad chest, and low posterior hairline.…”

“…In addition, structural cardiac abnormalities, gonadal dysgenesis, hypertension and diabetes are some of the secondary sex characteristics observed in patients with Turner syndrome [ 2 , 3 ]. Nearly 40–60% of TS patients have a 45,X karyotype, on the other hand, 45,X/46, XX; 46,X,i(Xq); and other variants are observed in several TS patients [ 1 ]. The gene responsible from short stature is found in the pseudoautosomal region 1 (PAR1), which is located on the short arm of the X chromosome and it is defined as the short stature homeobox-containing ( SHOX ) gene [ 4 ].…”

“…However, in recent years, molecular techniques such as polymerase chain reaction and single nucleotide polymorphism (SNP) genotyping have been used to detect sex chromosome abnormalities in a very short time with a low cost, using both blood and buccal samples. Especially with the recent improvements in technology, array comparative genomic hybridization (acGH) has been used to understand the genetic basis of Turner Syndrome [ 1 ].…”