Improved assay performance of single nucleotide polymorphism array over conventional karyotyping in analyzing products of conception.

BACKGROUND: Conventional karyotyping has been a routine method to identify chromosome abnormalities in products of conception. However, this process is being transformed by single nucleotide polymorphism (SNP) array, which has advantages over karyotyping, including higher resolution and dispensing with cell culture. Therefore, the purpose of this study was to evaluate the advantage of high-resolution SNP array in identifying genetic aberrations in products of conception. METHODS: We consecutively collected 155 products of conception specimens, including 139 from first-trimester miscarriage and 16 from second-trimester miscarriage. SNP array was performed on these samples in parallel with G-banded karyotyping. RESULTS: The test success rate was 98.1% (152/155) using SNP array, which was higher than that using karyotyping (133/155, 85.8%). It yielded a 63.8% (97/152) abnormality rate, and the frequency of various chromosome abnormalities was in agreement with other previous studies. The results between array and karyotyping demonstrated a 94.0% (125/133) concordance. SNP array obtained additional aberrations in 3.8% (5/133) of those cases unidentified by karyotyping, which included three cases with whole-genome uniparental disomy, one with pathogenic copy number variation, and one with del(4)(q35.1q35.2) and dup(12)(q24.31q24.33). However, chromosome translocations presented in two cases and tetraploidy presented in one case were detected by karyotyping instead of array. Additionally, two out of three cases with mosaic trisomy were revealed by array but recognized as pure trisomy by karyotyping. CONCLUSION: This study demonstrated that SNP array had certain advantages over G-banded karyotyping, including a higher success rate, additional detection of copy number variations and uniparental disomy, and improved sensitivity to mosaicism. Therefore, it would be an alternative method to karyotyping in clinical genetic practice.

[Investigation of ultrasound markers in screening fetal trisomy 21].

OBJECTIVE: To investigate the clinical value of ultrasound markers in screening fetal trisomy 21. METHODS: From Jan. 2001 to Dec. 2011, a retrospective study about sonographic information of 138 fetuses diagnosed as trisomy 21 was taken in the First Affiliated Hospital of Sun Yat-sen University. All fetuses were divided into 3 groups: isolated ultrasound markers, non-isolated ultrasound markers, and isolated structural malformations or other abnormalities. The relationship between trisomy 21 and ultrasound markers as well as structural anomalies or other abnormalities was analyzed. RESULTS: Sonographic anomalies were detected in 132 fetuses (95.7%, 132/138), including ultrasound markers and structural malformations or other abnormalities. One hundred and twenty cases (87.0%, 120/138) had ultrasound markers, 38 (31.7%, 38/120) had one marker and 82 (68.3%, 82/120) had more than one marker (P < 0.01). Fifty-one fetuses (37.0%, 51/138) had isolated ultrasound markers and non-isolated markers were found in 69 fetuses (50.0%, 69/138). Only 12 fetuses (8.7%, 12/138) had isolated structural malformations or other abnormalities. In 20 fetuses on whom the first-trimester ultrasound screening were performed, all had ultrasound markers, 95% (19/20) had thickened nuchal translucency and 55% (11/20) had nasal bone hypoplasia. The most common ultrasound markers on the second-trimester screening were nasal bone hypoplasia, which accounted for 41.9% (52/124) cases, followed by thickened nuchal fold (25.0%, 31/124), short femurs and humerus (24.2%, 30/124), echogenic intracardiac focus (16.1%, 20/124), mild ventriculomegaly (15.3%, 19/124), hyperechoic bowel (12.9%, 16/124), mild renal pyelectasis (12.1%, 15/124). Furthermore, the common structural malformations or other abnormalities were as follows: cardiac defects (33.1%, 41/124), digestive system (26.6%, 33/124). CONCLUSIONS: Ultrasound markers are valuable for screening fetal trisomy 21. The fetuses of trisomy 21 usually had more than one ultrasound markers or associated with other abnormalities. Combinations of ultrasound markers with the results of serum screening and maternal age are necessary for evaluation.

[Spectral karyotyping of seven prenatally detected marker chromosomes and complex chromosome aberrations].

OBJECTIVE: To perform spectral karyotyping (SKY), fluorescence in situ hybridization (FISH) and conventional karyotyping on prenatally detected marker chromosomes and complex chromosomal aberrations. METHODS: Five marker chromosomes and 2 complex chromosome aberrations diagnosed by G banding were collected. SKY was performed to verify the composition of marker chromosomes. FISH was used to confirm the diagnosis when necessary. In certain cases, C or N banding technique was employed to verify the composition of chromosomes. Results of ultrasonography and pregnancy outcome were reviewed. RESULTS: Among the 5 marker chromosomes, 2 were large and 3 were medium in size, 4 were de novo and one was inherited from the father. By SKY analysis, 2 marker chromosomes have originated from non-acrocentric chromosomes (4 and 9), whilst the other two have originated from acrocentric chromosomes (21 and 22). The remainder was derived from X chromosome. The SKY results were confirmed by FISH in 3 cases. Four cases have chosen to terminate the pregnancy after genetic counseling. A fetus with inherited paternal marker chromosome was delivered at term, and showed normal development during the first year of life. As for the other 2 cases with complex chromosome aberrations, by SKY examination, one had duplication in chromosome 8 and the other had chromosome rearrangements derived from translocation between chromosomes 2 and 6. In the latter case the fetus was delivered at term but showed developmental retardation at 6 months. CONCLUSION: SKY in combination with FISH can facilitate identification of the origins of marker chromosomes as well as complex chromosomal aberrations. With combined information from ultrasonography, SKY and FISH, effective counseling may be offered to the patients.

[Combined use of molecular cytogenetic techniques to detect a small chromosomal translocation].

OBJECTIVE: Comprehensive use of molecular cytogenetic techniques for the detection of 1 case of small chromosome translocation. METHODS: Following conventional chromosome preparation, G-banding karyotype analysis, spectral karyotyping (SKY), whole chromosome painting, two-color fluorescence in situ hybridization (FISH) and subtelomeric probe FISH were performed. RESULTS: G-banded karyotype was 46, XX, ?(22q11.3), SKY karyotype analysis was 46, XX, der (4)t(4;6) and found no abnormalities on chromosome 22, staining signal was not found with any abnormalities on chromosome 6. Two-color FISH indicated a chromosomal translocation segment of 22q13.3 to one end of the short arm of chromosome 4. Subtelomeric FISH probe showed the end of the long arm of chromosome 22 and the end of the short arm of chromosome 4 reciprocal translocation. High resolution G-banding and FISH result indicated 46, XX, t(4;22)(p15.3;q13.2). CONCLUSION: The testing of small chromosomal translocation should be combined with clinical information and integrated use of molecular cytogenetic techniques to improve the accuracy of diagnosis of chromosomal diseases.