Shaobin Lin

Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction.

To investigate the clinical value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of chromosomal abnormalities in fetal growth restriction (FGR) cases.

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.

Differing Microdeletion Sizes and Breakpoints in Chromosome 7q11.23 in Williams-Beuren Syndrome Detected by Chromosomal Microarray Analysis

Williams-Beuren syndrome (WBS) manifests as supravalvular aortic stenosis, intellectual disability, developmental delay and characteristic facial features. The common WBS deletion region ranges from 1.55 to 1.84 Mb and primarily contains the ELN gene. We analyzed 10 patients diagnosed with 7q11.23 microdeletion syndrome by chromosomal microarray analysis. The clinical features of these patients varied from classic WBS to normal phenotype. All 10 patients exhibited different sizes and breakpoints of chromosome microdeletions ranging from 44 kb to 9.88 Mb. The hemizygosity of the ELN gene was detected in 7 patients, while a normal ELN gene was present in 3 other patients with small deletions. We observed that the phenotypic features of WBS varied in fetuses, children and adults, influenced by the genes, deletion size and breakpoint. Our findings provide more information on the genotype-phenotype correlations of WBS. However, further research is needed to explore the size and breakpoint effect and functions of the genes on chromosome 7q11.23.

Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array

To evaluate the incidence and characteristics of unusual twinning by using single nucleotide polymorphism (SNP) array to identify twin zygosity.

Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia

To elucidate the relationship between copy number variations (CNVs) detected by high‐resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH).

Discordant phenotypes in monozygotic twins with 16p11.2 microdeletions including the SH2B1 gene

A 200∼240 kb SH2B1‐containing deletion region on 16p11.2 is associated with early‐onset obesity and developmental delay. Here, we describe monozygotic twin brothers with discordant clinical presentations. Intrauterine fetal growth restriction was present in both twins. Additionally, twin A exhibited coarctation of aorta, left ventricular noncompaction, atrial septal defect, pericardial effusion, left hydronephrosis, and moderate developmental delay, whereas twin B exhibited single umbilical artery. Chromosome microarray analysis was performed on both twins and their parents. An identical 244 kb microdeletion on 16p11.2 including 9 Refseq genes, including SH2B1, was identified in the twins. The novel findings in monozygotic twins may expand the phenotypic spectrum of 16p11.2 microdeletion. Further studies are needed to strengthen the correlation between genotypes and abnormal clinical features.

Chromosome 10q26 deletion syndrome: Two new cases and a review of the literature

The current study presents the cases of two unrelated patients with similar clinical features, including craniofacial anomalies, developmental delay/intellectual disability and cardiac malformations, that are consistent with chromosome 10q26 deletion syndrome. High-resolution single-nucleotide polymorphism analysis revealed that 10q26 terminal deletions were present in these two patients. The locations and sizes of the 10q26 deletions in these two patients were compared with the locations and sizes of 10q26 deletions in 30 patients recorded in the DECIPHER database and 18 patients characterized in previous studies through chromosomal microarray analysis. The clinical features and locations of the 10q26 deletions of these patients were reviewed in an attempt to map or refine a critical region (CR) for phenotypes. Additionally, the association between previously suggested CRs and phenotypic variability was discussed. The current study emphasize that a distal 10q26 terminal deletion with a breakpoint at ~130 Mb may contribute to the common clinical features of 10q26 deletion syndrome.

Cytogenetic and molecular study of a patient with severe oligozoospermia and asthenozoospermia

OBJECTIVE To explore genetic etiologies of a patient with severe oligozoospermia and asthenozoospermia. METHODS G-banded karyotyping and fluorescence in situ hybridization (FISH) were used to characterize the origin and structure of the abnormal chromosome discovered in this patient. Multiplex polymerase chain reaction (PCR) was used to detect microdeletion of azoospermia factor (AZF). RESULTS G-banding revealed a karyotype of 45,X,der(15) (?::p11.2→ qter)dn for the patient. Dual-color FISH confirmed that SRY gene was present in a segment attached to the short arm of chromosome 15. Sex chromosome mosaicism and numerical abnormality therefore were both present. Dual-color FISH revealed karyotype of nuc ish(DXZ1× 1, SRY× 1)[390/400]/(DXZ1× 2, SRY× 1) [10/400]. Four-color FISH showed that the abnormal chromosome 15 has derived from a pseudodicentric (Y;15) translocation, and that the breakpoint on Y chromosome was located at Yq12. G-banding and FISH results confirmed that the karyotype was 45,X,der(15)(?::p11.2→ qter)dn.ish psu dic(15;Y)(p11.2;q12)(D15Z1+ , SNRPN+ , PML+ ; SRY+ , DYZ3+ , DYZ1+ ). Microdeletion of AZFc combined with sY254 deletion was detected by multiplex PCR. CONCLUSION Cytogenetic and molecular genetic analysis of the patient has indicated meiotic disturbances with spermatogenetic arrest resulting from a pseudodicentric chromosome derived from Y;15 translocation and spermatogenesis dysfunction resulting from partial deletion of AZFc region.

Chromosomal aberrations and CNVs in twin fetuses with cardiovascular anomalies: Comparison between monochorionic diamniotic and dichorionic diamniotic twins

To investigate the types of cardiovascular anomalies and the results of invasive prenatal diagnosis in twin fetuses.

Intrauterine phenotypic features associated with 16p11.2 recurrent microdeletions

To investigate the detection rate of 16p11.2 recurrent microdeletions in fetuses with abnormal ultrasound findings and determine the common abnormal ultrasound findings in fetuses carrying the deletion.