[Genetic analysis and assisted reproductive guidance for two infertile patients with rare small supernumerary marker chromosomes].

OBJECTIVE: To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC). METHODS: Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. RESULTS: For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47,XY,del(16)(p10p12),+mar[65]/46,XY,del(16)(p10p12)[6]/48,XY,del(16)(p10p12),+2mar[3].ish mar(Tel 16p-,Tel 16q-,CEP 16-,WCP 16+). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47,XX,+mar[37]/46,XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5:g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). CONCLUSION: For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

A case report of a normal fertile woman with 46,XX/46,XY somatic chimerism reveals a critical role for germ cells in sex determination.

Individuals with 46,XX/XY chimerism can display a wide range of characteristics, varying from hermaphroditism to complete male or female, and can display sex chromosome chimerism in multiple tissues, including the gonads. The gonadal tissues of females contain both granulosa and germ cells. However, the specific sex chromosome composition of the granulosa and germ cells in 46,XX/XY chimeric female is currently unknown. Here, we reported a 30-year-old woman with secondary infertility who displayed a 46,XX/46,XY chimerism in the peripheral blood. FISH testing revealed varying degrees of XX/XY chimerism in multiple tissues of the female patient. Subsequently, the patient underwent preimplantation genetic testing (PGT) treatment, and 26 oocytes were retrieved. From the twenty-four biopsied mature oocytes, a total of 23 first polar bodies (PBs) and 10 second PBs were obtained. These PBs and two immature metaphase I (MI) oocytes only displayed X chromosome signals with no presence of the Y, suggesting that all oocytes in this chimeric female were of XX germ cell origin. On the other hand, granulosa cells obtained from individual follicles exhibited varied proportions of XX/XY cell types, and six follicles possessed 100% XX or XY granulosa cells. A total of 24 oocytes were successfully fertilized, and 12 developed into blastocysts, where 5 being XY and 5 were XX. Two blastocysts were transferred with one originating from an oocyte aspirated from a follicle containing 100% XY granulosa cells. This resulted in a twin pregnancy. Subsequent prenatal diagnosis confirmed normal male and female karyotypes. Ultimately, healthy boy-girl twins were delivered at full term. In summary, this 46,XX/XY chimerism with XX germ cells presented complete female, suggesting that germ cells may exert a significant influence on the sexual determination of an individual, which provide valuable insights into the intricate processes associated with sexual development and reproduction.

A comparison of neurological event and mortality rates between transcatheter aortic valve implantation and surgical aortic valve replacement.

Introduction: Transcatheter aortic valve implantation (TAVI) is the treatment of choice for patients with symptomatic severe aortic stenosis. Aim: To evaluate the neurological event and mortality rates of TAVI in comparison with those of surgical aortic valve replacement (SAVR). Material and methods: A systematic literature search identified pertinent full-text journal articles published from 2000 to 2022 that were taken as the study materials. Results: Patients were at the age of 79.3 ±2.8 years and 79.9 ±2.9 years at the time of intervention/open surgery in the TAVI and SAVR groups, respectively. Patients' age and preoperative comorbidity rates were similar in both groups. A self-expanding valve prosthesis and a percutaneous transfemoral route were the most commonly used in patients receiving TAVI. The duration of the procedure and the hospital stay were much shorter, and the number of transfused blood units was much lower in the TAVI group than in the SAVR group. No significant intergroup difference was found in the prevalence of postoperative stroke, 1-month all-cause mortality, and 1-month and 1-year cardiovascular mortality rates. However, 1-year all-cause mortality was much lower in the TAVI than the SAVR group. The subgroups of risk stratification showed better outcomes for non-high-risk patients compared with high-risk patients. Conclusions: Irrespective of other postoperative complications of TAVI, this study emphasizes the postoperative major neurological events and mortality. TAVI appears to be superior to SAVR with regard to 1-year all-cause mortality. TAVI is thus recommended for elderly patients with symptomatic severe aortic stenosis at very high surgical risk contraindicated for SAVR.

Tracheal Bronchus in Children.

Tracheal bronchus is an uncommon congenital anomaly. It is often of important significance during endotracheal intubation. In paediatrics with tracheal bronchus, stenosis of trachea and (or) bronchus and the management strategies remain to be further clarified. A comprehensive retrieval of literature since 2000 revealed 43 articles with 334 paediatric patients with tracheal bronchus. The delayed diagnosis rate is 4.1%. Paediatric patients with tracheal bronchus most often present with recurrent pneumonia and atelectasis. In less than one-third of the patients, there was an intrinsic or extrinsic stenosis of the trachea, which warrant a conservative or a surgical treatment. A surgical treatment was performed in 15.3% of the patients, in most of which the operations were for relieving the tracheal stenosis. The surgical outcomes were satisfactory. Paediatric patients with tracheal bronchus with tracheal stenosis and recurrent pneumonia and persistent atelectasis warrant active treatments, and surgical treatments are preferred. No treatment is needed in those with no tracheal stenosis or those with no or mild symptoms. Key Words: Abnormality, Congenital, Thoracic surgery, Tracheal stenosis.

Right Atrial Tumour Thrombus in Advanced Hepatocellular Carcinoma: Surgical Techniques and Prognosis.

Hepatocellular carcinoma (HCC) with right atrium (RA) tumour thrombus is a rare condition but the treatment always poses challenges. Debates remain with regard to the use of cardiopulmonary bypass (CPB) in the surgical procedures. The aim of the present review was to summarise the surgical procedures of RA tumour thrombus removal and to discuss the pertinent indications. Twenty-three articles involving 35 patients were collected and recruited into this study. Surgical operation for HCC was performed in 29 (82.9%) patients and non-surgical operation in 6 (17.1%) patients. RA tumour thrombus removal was performed with the aid of CPB in 25 (71.4%), venovenous bypass in 3 (8.6%), and without CPB in 7 (20%) patients. After tumour thrombus removal, RA or vessel wall reconstruction with a graft was required in 7 (20%) patients. The overall median survival time of this patient cohort was 30.8 months. The median survival time of patients who received a hepatectomy was 30.5 months, in comparison to 6.0 months for those who did not receive a hepatectomy. Aggressive surgical treatment prolongs survival of selective patients with HCC with RA tumour thrombus. CPB is helpful for complete removal of the tumour thrombus from the RA. In patients with tumour thrombus invading the RA or vessel walls, a graft repair is warranted. Key Words: Hepatocellular carcinoma, Inferior vena cava, Right atrium, Tumour thrombus.

Analysis of GJB2 gene mutations spectrum and the characteristics of individuals with c.109G>A in Western Guangdong.

BACKGROUND: GJB2 mutations are among the most important causes of deafness, and their prevalence varies greatly among different countries and ethnic groups. This study aimed to determine the pathogenic mutation spectrum of GJB2 in patients with nonsyndromic hearing loss (NSHL) in Western Guangdong and to explore the pathogenic characteristics of the c.109G>A locus. METHODS: In total, 97 NSHL patients and 212 normal controls (NC) were included in this study. Genetic sequencing analyses were performed on GJB2. RESULTS: In the NSHL group, the main pathogenic mutations in GJB2 were as follows: c.109G>A, c.235delC, and c.299_300delAT with allele frequencies of 9.28%, 4.12%, and 2.06%, respectively. c.109G>A was the most frequently detected pathogenic mutation in this region. In the NC group, the allele frequency of c.109G>A among 30-50 years old subjects was markedly lower than that among 0-30 years old subjects (5.31% vs. 11.11%, p < 0.05). CONCLUSION: We found the pathogenic mutation spectrum of GJB2 in this region and showed that c.109G>A was the most common GJB2 mutation with unique characteristics, such as clinical phenotypic heterogeneity and delayed onset. Therefore, the c.109G>A mutation should be considered as an essential marker for routine genetic assessment of deafness, which can also be beneficial for preventing deafness.

Mycotic subclavian artery aneurysms: a scoping review.

Introduction: Mycotic subclavian artery aneurysms (SAAs) are a very rare disorder. Aim: To provide an overview of current knowledge on clinical features, management strategies and outcome evaluations of mycotic SAAs. Material and methods: The study materials were based on comprehensive literature retrieval of publications of mycotic SAAs published between 2000 and 2023. Results: Contaminated mechanical injuries and abscess erosions of the arterial walls are mechanisms of mycotic SAAs. The diagnosis relies on detection of pathogenic microorganisms by cultures or microbiological investigations of blood, other fluids and infected tissues as well as medical imaging visualization. The indications for an interventional therapy were poor general condition, high surgical risk, and rescue exclusion for a ruptured pseudoaneurysm. Three (9.1%) pre-treatment deaths were a result of sudden rupture of the mycotic SAAs and thus they lost the opportunity of treatment. All post-treatment deaths occurred in the interventional patient group, whereas the causes of death seemed to be unrelated to mycotic SAAs per se or to treatments of choice. Patient outcome evaluations revealed no significant difference between different treatments of choice. No significant predictive risk factors were responsible for patient outcomes. Conclusions: Once a diagnosis of mycotic SAA is made, sensitive antibacterial drugs are applied immediately to control the infection and control aneurysmal progression. Early treatment is conducted as soon as possible to avoid aneurysmal rupture. A decision on treatment of choice is made based on the patient's specific condition. Antibacterial drug use is continued for about 6 weeks after surgical or interventional therapy.

Sternal Fractures due to Blunt Chest Trauma.

The present article aimed to give an overview of sternal fractures and discuss their management and prognoses. The retrieved pertinent publications of 2011-2021 constituted the materials of the present study. The misdiagnosis rate of X-ray was 5.5% and that of sonography was 6.3% for diagnosing the sternal fractures. There were more patients with complicated than with isolated sternal fractures (98.8% vs. 1.2%, p<0.001). Sternal fractures were treated surgically in 59.5%, conservatively in 39.7%, and staged conservatively and surgically in 0.8% of patients. Extremity fractures, brain injury, lung contusion, and intraabdominal/intraperitoneal injuries were the most common associated injuries to sternal fractures. A small number of patients with sternal fractures have fracture-related delayed complications, most of which require surgical treatments with good outcomes. For solitary sternal fractures, short-term pain relief is sufficient. Most complicated sternal fractures require surgical treatment by sternal fixation. Intrathoracic injuries, especially life-threatening cardiopulmonary injuries that are complicated to sternal fractures warrant resuscitation and corresponding active treatment. The causes of patients' death with sternal fractures were usually not related to the sternum fracture itself, but mostly to the associated injuries. Key Words: Fracture, Sternum, Trauma.

Percutaneous closure of left ventricular pseudoaneurysm.

The aim of the present study is to describe the indications, treatment effects, and patient outcomes of percutaneous management of left ventricular pseudoaneurysm (LVPA). The study materials were based on comprehensive literature retrieval since 2004. The mechanisms of LVPA formation can be divided into surgical, percutaneous, and medial disease related. Of the surgical mechanisms, coronary artery bypass grafting prevailed. The formation time was the longest in medical disease-related LVPAs up to 44.4 months. The percutaneous procedures succeeded on the first try in 79 (84.9%) patients, whereas failures were encountered during the percutaneous manoeuvres in 14 (15.1%) patients. Percutaneous closure of LVPA was especially indicated for patients carrying a high surgical risk. The iatrogenic traumas, such as left ventricular venting, should be avoided to prevent this complication. The preliminary cut-off valves of oversize 3.3 mm and oversize ratio 1.6 should be followed for reference for device choice.

Pulmonary artery pathologies in Alagille syndrome: a meta-analysis.

Alagille syndrome, caused by mutations in the gene encoding Jagged1 (JAG1), a ligand in the Notch signaling pathway, is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, face and skeleton. The aim of the present study is try to disclose the clinical features, management and outcomes of pulmonary artery stenosis associated with Alagille syndrome. By comprehensive literature retrieval, 38 articles involving 401 patients were recruited for this study. The pertinent variables closely related to pulmonary artery stenosis in patients with Alagille syndrome were comprehensively analyzed by following the PRISMA guidelines. The management of pulmonary artery pathologies, especially a severe type of pulmonary artery stenosis in Alagille syndrome, is a concerned matter. Publications of literature retrieval of recent 3 decades were the study material of this article. The pulmonary artery pathologies, especially the severe type of pulmonary artery stenosis in Alagille syndrome, warrant surgical or interventional treatments. After the procedures, the right ventricular to left ventricular pressure ratio was reduced by 25%. There were no intergroup differences in terms of recovery, reintervention and mortality rates between interventionally and surgically treated patients. Transcatheter treatment is preferable due to less trauma. Surgical treatment of pulmonary artery stenosis can be performed currently with intracardiac defect repair.

The de novo aberration rate of prenatal karyotype was comparable between 1496 fetuses conceived via IVF/ICSI and 1396 fetuses from natural conception.

PURPOSE: To evaluate the cytogenetic risk of assisted reproductive technology (ART) by comparing the incidence of de novo chromosomal abnormalities between fetuses conceived via in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and natural conception. MATERIALS AND METHODS: Prenatal invasive diagnostic testing (amniocentesis and cytogenetic analysis) was performed on 1496 fetuses conceived via IVF/ICSI (IVF/ICSI group) and 1396 fetuses from natural conception (NC group). The incidence of de novo chromosomal abnormalities (including aneuploidy and chromosomal structure abnormalities) was used to evaluate the cytogenetic risk of ART. For statistical analysis, χ2-test was used for binary dependent variable. The significance level was P < 0.05 and confidence interval was 95%. RESULT(S): The IVF/ICSI group displayed a modest increase in the overall de novo chromosomal abnormality rate compared with that in the NC group but with no statistical significance (6.75% vs. 6.16%; χ2 = 0.42, P > 0.05). The incidence of abnormal karyotypes was also not significantly different between the IVF/ICSI and NC groups in different maternal ages, including ≥ 35 years group (7.55% vs. 9.60%, χ2 = 1.40, P > 0.05) and < 35 years group (6.20% vs. 4.54%, χ2 = 2.51, P > 0.05). Moreover, there was no difference in the proportion of aneuploid and structural abnormalities in detected karyotypes between the IVF/ICSI and NC groups. Logistic regression analysis showed no significant association between the method of pregnancy and de novo chromosomal abnormalities (odds ratio (OR) 1.03; 95% CI 0.71-1.50; P = 0.86) after adjusting for other confounding factors. CONCLUSION(S): Fetuses conceived via IVF/ICSI had a slight but not statistically significant increase in de novo abnormal karyotypes compared to those in naturally conceived fetuses. Our findings indicate no significant association between de novo fetal chromosomal abnormalities and the pregnancy method in high-risk pregnancies in the second trimester. For these pregnancies with a high risk but with a normal karyotype, further genetic testing is required for diagnosis.

Surgical treatment of renal cell carcinoma with inferior vena cava tumor thrombus.

PURPOSE: The present report discusses the indications of cardiopulmonary bypass (CPB) in open nephrectomy and surgical outcomes of conventional and minimally invasive surgical techniques for treating advanced renal cell carcinoma with inferior vena cava tumor thrombus. METHODS: The present study involved a comprehensive retrieval of pertinent literature from the most recent two decades. RESULTS: Comparisons between radical nephrectomy procedures in terms of open, laparoscopic and robotic-assisted surgeries revealed that open surgery had more blood loss, a longer operation time and higher mortality rates than laparoscopic and robotic-assisted surgeries. Furthermore, surgery with CPB was associated with more blood loss than non-CPB surgery. Rates of early and late deaths were much higher in patients with CPB than in those without CPB. CONCLUSIONS: Different surgical techniques had different indications in terms of levels of inferior vena cava tumor thrombus. The laparoscopic, robotic-assisted, open surgical techniques and CPB with deep hypothermic circulatory arrest were indicated for Levels I, II, III and III-IV inferior vena cava tumor thrombus, respectively. Laparoscopic and robotic-assisted surgeries cause less trauma than open surgery but require more complicated equipments to support the procedure. CPB should be avoided in radical nephrectomy whenever possible. The increased application of laparoscopic and robotic techniques in the future is anticipated.

Catheter ablation for tachyarrhythmias during pregnancy.

Introduction: Refractory arrhythmias during pregnancy pose challenges to physicians. Aim: To give an overview of catheter ablation for tachyarrhythmias during pregnancy, and to discuss the indications of the procedure and the outcomes of both mother and fetus. Material and methods: The study materials were based on comprehensive literature retrieval of the pertinent articles published since 2000. Results: The indications for catheter ablation were refractory arrhythmias unresponsive to drug therapy in most of the cases followed by requirement of cardioversion. Atrioventricular nodal reentrant tachycardia was the most common arrhythmia developed during pregnancy. Pregnancy complications were present in 2.4% of the cases. There was no mortality among the pregnant patients. Fetal adverse events occurred in 3.1% of the cases, more in the fluoroscopy than in the zero-fluoroscopy group. The patient cohort with a radiation dose of > 50 mGy in one-third of the cases had a 14.3% fetal adverse event rate. Fetal adverse events occurred only in the second trimester, not in the other two trimesters. Conclusions: Drug-refractory and poorly tolerated tachycardias in pregnant patients warrant catheter ablation. Zero-fluoroscopy technique under guidance with three-dimensional mapping systems is preferred and strict minimal fluoroscopy is only used in extreme necessity. As ablation in the second trimester was associated with a probable higher fetal adverse event rate, it is suggested that ablation is preferably performed in the third trimester.

Next-generation sequence-based preimplantation genetic testing for monogenic disease resulting from maternal mosaicism.

BACKGROUND: Mosaicism poses challenges for genetic counseling and preimplantation genetic testing for monogenic disorders (PGT-M). NGS-based PGT-M has been extensively used to prevent the transmission of monogenic defects, but it has not been evaluated in the application of PGT-M resulting from mosaicism. METHODS: Four women suspected of mosaicism were confirmed by ultra-deep sequencing. Blastocyst trophectoderm cells and polar bodies were collected for whole genome amplification, followed by pathogenic variants detection and haplotype analysis based on NGS. The embryos free of the monogenic disorders were transplantable. RESULTS: Ultra-deep sequencing confirmed that the four women harbored somatic mosaic variants, with the proportion of variant cells at 1.12%, 9.0%, 27.60%, and 91.03%, respectively. A total of 25 blastocysts were biopsied and detected during four PGT cycles and 5 polar bodies were involved in one cycle additionally. For each couple, a wild-type embryo was successfully transplanted and confirmed by prenatal diagnosis, resulting in the birth of four healthy infants. CONCLUSIONS: Mosaic variants could be effectively evaluated via ultra-deep sequencing, and could be prevented the transmission by PGT. Our work suggested that an NGS-based PGT approach, involving pathogenic variants detection combined with haplotype analysis, is crucial for accurate PGT-M with mosaicism.

Reproductive risks and preimplantation genetic testing intervention for X-autosome translocation carriers.

RESEARCH QUESTION: What is the genetic cause of multiple congenital disabilities in a girl with a maternal balanced X-autosome translocation [t(X-A)]? Is preimplantation genetic testing (PGT), to distinguish non-carrier from euploid/balanced embryos and prioritize transfer, an effective and applicable strategy for couples with t(X-A)? DESIGN: Karyotype analysis, whole-exome sequencing and X inactivation analysis were performed for a girl with congenital cardiac anomalies, language impairment and mild neurodevelopmental delay. PGT based on next-generation sequencing after microdissecting junction region (MicroSeq) to distinguish non-carrier and carrier embryos was used in three couples with a female t(X-A) carrier (cases 1-3). RESULTS: The girl carried a maternal balanced translocation 46,X,t(X;1)(q28;p31.1). Whole-exome sequencing revealed no monogenic mutation related to her phenotype, but she carried a rare skewed inactivation of the translocated X chromosome that spread to the adjacent interstitial 1p segment, contrary to her mother. All translocation breakpoints in cases 1-3 were successfully identified and each couple underwent one PGT cycle. Thirty oocytes were retrieved, and 13 blastocysts were eligible for biopsy, of which six embryos had a balanced translocation and only four were non-carriers. Three cryopreserved embryo transfers with non-carrier status embryos resulted in the birth of two healthy children (one girl and one boy), who were subsequently confirmed to have normal karyotypes. CONCLUSIONS: This study reported a girl with multiple congenital disabilities associated with a maternal balanced t(X-A) and verified that the distinction between non-carrier and carrier embryos is an effective and applicable strategy to avoid transferring genetic and reproductive risks to the offspring of t(X-A) carriers.

Clinical outcomes following preimplantation genetic testing and microdissecting junction region in couples with balanced chromosome rearrangement.

PURPOSE: The purpose of this study is to summarize the clinical outcomes of apparently balanced chromosome rearrangement (ABCR) carriers in preimplantation genetic testing (PGT) cycles by next-generation sequencing following microdissecting junction region (MicroSeq) to distinguish non-carrier embryos from balanced carriers. METHODS: A retrospective study of 762 ABCR carrier couples who requested PGT for structural rearrangements combined with MicroSeq at the Reproductive and Genetic Hospital of CITIC-Xiangya was conducted between October 2014 and October 2019. RESULTS: Trophectoderm biopsy was performed in 4122 blastocysts derived from 917 PGT-SR cycles and 3781 blastocysts were detected. Among the 3781 blastocysts diagnosed, 1433 (37.9%, 1433/3781) were balanced, of which 739 blastocysts were carriers (51.57%, 739/1433) and 694 blastocysts were normal (48.43%, 694/1433). Approximately 26.39% of cycles had both carrier and normal embryo transfer, and the average number of biopsied blastocysts was 6.7. In the cumulative 223 biopsied cycles with normal embryo transfer, all couples chose to transfer the normal embryos. In the 225 cycles with only carrier embryos, the couples chose to transfer the carrier embryos in 169/225 (75.11%) cycles. A total of 732 frozen embryo transfer cycles were performed, resulting in 502 clinical pregnancies. Cumulatively, 326 babies were born; all of these babies were healthy and free of any developmental issues. CONCLUSION: Our study provides the first evaluation of the clinical outcomes of a large sample with ABCR carrier couples undergoing the MicroSeq-PGT technique and reveals its powerful ability to distinguish between carrier and non-carrier balanced embryos.

The genetic cause of intellectual deficiency and/or congenital malformations in two parental reciprocal translocation carriers and implications for assisted reproduction.

PURPOSE: To elucidate the genetic cause of intellectual deficiency and/or congenital malformations in two parental reciprocal translocation carriers and provide appropriate strategies of assisted reproductive therapy (ART). MATERIALS AND METHODS: Two similar couples having a child with global developmental delay/intellectual disability symptoms attended the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) in 2017 and 2019, respectively, in order to determine the cause(s) of the conditions affecting their child and to seek ART to have a healthy baby. Both of the healthy couples were not of consanguineous marriage, denied exposure to toxicants, and had no adverse life history. This study was approved by the Institutional Ethics Committee of the Reproductive & Genetic Hospital of CITIC-Xiangya, and written informed consent was obtained from the parents. Genetic diagnoses were performed by karyotype analysis, breakpoint mapping analysis of chromosomal translocation(s), single-nucleotide polymorphism (SNP) microarray analysis, and whole-exome sequencing (WES) for the two children and different appropriate reproductive strategies were performed in the two families. RESULTS: Karyotype analysis revealed that both patients carried parental reciprocal translocations [46,XY,t(7;16)(p13;q24)pat and 46,XY,t(13;17)(q12.3;p11.2)pat, respectively]. Follow-up breakpoint mapping analysis showed no interruption of associated genes, and SNP microarray analysis identified no significant copy number variations (CNVs) in the two patients. Moreover, WES results revealed that patients 1 and 2 harbored candidate compound heterozygous mutations of MCOLN1 [c.195G>C (p.K65N) and c.1061G>A (p.W354*)] and MCPH1 [c.877A>G (p.S293G) and c.1869_1870delAT (p.C624*)], respectively, that were inherited from their parents and not previously reported. Furthermore, the parents of patient 1 obtained 10 embryos during ART cycle, and an embryo of normal karyotype and non-carrier of observed MCOLN1 mutations according to preimplantation genetic testing for structural rearrangement and monogenic defect was successfully transferred, resulting in the birth of a healthy boy. The parents of patient 2 chose to undergo ART with donor sperm to reduce the risk of recurrence. CONCLUSIONS: Systematic genetic diagnosis of two carriers of inherited chromosomal translocations accompanied by clinical phenotypes revealed their cause of disease, which was critical for genetic counseling and further ART for these families.

Novel homozygous truncating variants in ZMYND15 causing severe oligozoospermia and their implications for male infertility.

Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.37%) unrelated patients with SO, including c.1209T>A(p.Tyr403*), c.1650delC (p.Glu551Lysfs*75), and c.1622_1636delinsCCAC (p.Leu541Profs*39). In silico bioinformatic analyses as well as in vivo and in vitro experiments showed that the ZMYND15 variants carried by the affected subjects might be the underlying cause for their infertility. One patient accepted intracytoplasmic sperm injection therapy, using his ejaculated sperm, and his wife successfully became pregnant. Our findings expand the disease phenotype spectrum by indicating that ZMYND15 variants cause SO and male infertility and suggest a possible correlation between the severity of male infertility caused by ZMYND15 variants and male age.

Hoarseness Due to Aortic Arch Aneurysms.

OBJECTIVE: To give an overview of the Ortner's syndrome caused by an aortic arch aneurysm. METHODS: By comprehensive retrieval of the pertinent literature published in the past two decades, 75 reports including 86 patients were collected and recruited into this study along with a recent case of our own. RESULTS: The aortic arch aneurysms causing hoarseness were most commonly mycotic aneurysms. In this patient setting, in addition to the left recurrent laryngeal nerve, trachea was the most commonly affected structure by the aortic arch aneurysm. Surgical/interventional/hybrid treatments led to a hoarseness-relieving rate of 64.3%, much higher than that of patients receiving conservative treatment. However, hoarseness recovery took longer time in the surgically treated patients than in the interventionally treated patients. CONCLUSION: The surgical and interventional treatments offered similar hoarseness-relieving effects. Surgical or interventional treatment is warranted in such patients for both treatment of arch aneurysms and relief of hoarseness.