Identification and interruption of inheritance of familial cryptic translocations: A case report.

Background: Cryptic translocations can be identified via genetic analysis of aborted tissues or malformed infants, but it is difficult to deduce the parental origins of the translocations. In the absence of such information, it is not easy to distinguish translocations from normal embryos during pre-implantation genetic testing, that seeks to block familial transmission of translocations.

Methods: Here, we present a new method that detects cryptic translocations and blocks familial transmission thereof.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood.

Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion.

Highly precise breakpoint detection of chromosome balanced translocation in chronic myelogenous leukaemia: Case series.

Chronic myelogenous leukaemia (CML) has a special phenomenon of chromosome translocation, which is called Philadelphia chromosome translocation. However, the detailed connection of this structure is troublesome and expensive to be identified. Low-coverage whole genome sequencing (LCWGS) could not only detect the previously unknown chromosomal translocation, but also provide the breakpoint candidate small region (with an accuracy of ±200 bases).

Analysis of complex chromosomal rearrangements using a combination of current molecular cytogenetic techniques.

Background: Using combined fluorescence in situ hybridization (FISH) and high-throughput whole-genome sequencing (WGS) molecular cytogenetic technology, we aim to analyze the junction breakpoints of complex chromosome rearrangements (CCR) that were difficult to identify by conventional karyotyping analysis and further characterize the genetic causes of recurrent spontaneous abortion.

Results: By leveraging a combination of current molecular techniques, including chromosome karyotype analysis, FISH, and WGS, we comprehensively characterized the extremely complex chromosomal abnormalities in this patient with recurrent spontaneous abortions. Here, we demonstrated that combining these current established molecular techniques is an effective and efficient workflow to identify the structural abnormalities of complex chromosomes and locate the rearrangement of DNA fragments.

A de novo 10q11.23q22.1 deletion detected by whole genome mate-pair sequencing: a case report.

Background: Interstitial deletions of chromosome band 10q11-q22 was a genomic disorder distinguished by developmental delay, congenital cleft palate and muscular hypotonia. The phenotypes involved were heterogeneous, hinge on the variable breakpoints and size.

Case Presentation: Here, we presented a patient with soft palate cleft, growth and development delay.

Successful birth after preimplantation genetic testing for a couple with two different reciprocal translocations and review of the literature.

Background: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is widely applied in couples with single reciprocal translocation to increase the chance for a healthy live birth. However, limited knowledge is known on the data of PGT-SR when both parents have a reciprocal translocation. Here, we for the first time present a rare instance of PGT-SR for a non-consanguineous couple in which both parents carried an independent balanced reciprocal translocation and show how relevant genetic counseling data can be generated.

Breakpoints Identification of a Balanced Complex Chromosome Rearrangement Case: 46,XX, t(6;15;10;9)(q13;q15;p11.2;q34.3) ins(9;8)(q22.33;q21.1q21.3).

Background: Balanced complex chromosome rearrangement (CCR) carriers are phenotypically normal but at high risk of reproductive failure, recurrent miscarriages, and affected offspring, so that cytogenetic characterizations of CCR carriers are crucial.

Methods: We report a case of CCR: 46,XX, t(6;15;10;9)(q13;q15;p11.2;q34.

A case report of congenital idiopathic hypogonadotropic hypogonadism caused by novel mutation of GNRHR gene.

Rationale: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree.

Patient Concerns: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development.

Diagnoses: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH.

Successful pregnancy after prenatal diagnosis by NGS for a carrier of complex chromosome rearrangements.

Background: The study is aimed to provide prediction for fertility risk in the setting of assisted reproduction for a woman with complex chromosomal rearrangements (CCRs).

Methods: We implemented a robust approach, which combined whole-genome low-coverage mate-pair sequencing (WGL-MPS), junction-spanning PCR and preimplantation genetic testing for aneuploidy (PGT-A) method to provide accurate chromosome breakpoint junctional sequences in the embryo selection process in the setting of assisted reproduction for a couple with recurrent abortions due to CCRs.

Result: WGL-MPS was applied to a female carrying CCRs which consisted of 9 breakpoints and 1 cryptic deletion related to fertility risks.

Screening of triploid with low-coverage whole-genome sequencing by a single-nucleotide polymorphism-based test in miscarriage tissue.

Purpose: To establish a single-nucleotide polymorphism-based analysis (SBA) method to identify triploidy in the miscarriage tissue by using low-coverage whole-genome sequencing (LC-WGS).

Methods: The method was established by fitting a quadratic curve model by counting the distribution of three heterozygous mutation content intervals. The triploid test result was mainly determined by the opening direction and the axis of symmetry of the quadratic curve, and Z test between the same batch samples was also used for auxiliary judgment.

Serum CEA and CA19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia.

Background: High concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were found in the serum of patients with colon cancer. We performed the present work to investigate the association between elevated levels of serum biomarkers (CEA and CA19-9) and shortened survival in patients with colon cancer.

Methods: We examined patients who underwent colonoscopies between 2001 and 2014 and measured and analyzed the serum CEA and CA19-9 levels of 362 participants.

Maternal interchromosomal insertional translocation leading to 1q43-q44 deletion and duplication in two siblings.

Background: 1q43-q44 deletion syndrome is a well-defined chromosomal disorder which is characterized by moderate to severe mental retardation, and variable but characteristic facial features determined by the size of the segment and the number of genes involved. However, patients with 1q43-q44 duplication with a clinical phenotype comparable to that of 1q43-q44 deletion are rarely reported. Moreover, pure 1q43-q44 deletions and duplications derived from balanced insertional translocation within the same family with precisely identified breakpoints have not been reported.

Breakpoints and deleted genes identification of ring chromosome 18 in a Chinese girl by whole-genome low-coverage sequencing: a case report study.

Background: Ring chromosome 18 [r(18)] is formed by 18p- and 18q- partial deletion and generates a ring chromosome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific phenotype, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion. The aim of this study is to identify the detailed breakpoints location and the deleted genes result from the r18.

Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR.

Intragenic and extragenic disruptions of FOXL2 mapped by whole genome low-coverage sequencing in two BPES families with chromosome reciprocal translocation.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder that affects craniofacial development and ovarian function. FOXL2 is the only gene known to be responsible for BPES. The majority of BPES patients show intragenic mutations of FOXL2.

Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male.

It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in the azoospermic male; however, the exact genetic damages are currently unknown for more than 40% of azoospermia. To elucidate the causative gene defects, we used the next generation sequencing (NGS) to map the breakpoints of a chromosome insertion from an azoospermic male who carries a balanced, maternally inherited karyotype 46, XY, inv ins (18,7) (q22.

A robust approach for blind detection of balanced chromosomal rearrangements with whole-genome low-coverage sequencing.

Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next-generation sequencing has been reported to detect BCA-associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application.

Complete genome sequencing and variant analysis of a Pakistani individual.

We sequenced the genome of a Pakistani male at 25.5x coverage using massively parallel sequencing technology. More than 90% of the sequence reads were mapped to the human reference genome.