Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

Chromosome karyotyping is a critical way to diagnose various hematological malignancies and genetic diseases, of which chromosome detection in raw metaphase cell images is the most critical and challenging step. In this work, focusing on the joint optimization of chromosome localization and classification, we propose ChromTR to accurately detect and classify 24 classes of chromosomes in raw metaphase cell images. ChromTR incorporates semantic feature learning and class distribution learning into a unified DETR-based detection framework. Specifically, we first propose a Semantic Feature Learning Network (SFLN) for semantic feature extraction and chromosome foreground region segmentation with object-wise supervision. Next, we construct a Semantic-Aware Transformer (SAT) with two parallel encoders and a Semantic-Aware decoder to integrate global visual and semantic features. To provide a prediction with a precise chromosome number and category distribution, a Category Distribution Reasoning Module (CDRM) is built for foreground-background objects and chromosome class distribution reasoning. We evaluate ChromTR on 1404 newly collected R-band metaphase images and the public G-band dataset AutoKary2022. Our proposed ChromTR outperforms all previous chromosome detection methods with an average precision of 92.56% in R-band chromosome detection, surpassing the baseline method by 3.02%. In a clinical test, ChromTR is also confident in tackling normal and numerically abnormal karyotypes. When extended to the chromosome enumeration task, ChromTR also demonstrates state-of-the-art performances on R-band and G-band two metaphase image datasets. Given these superior performances to other methods, our proposed method has been applied to assist clinical karyotype diagnosis.
Humans ; Metaphase ; Karyotyping/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Chromosomes, Human/genetics*

The probiotic strain Escherichia coli Nissle 1917 (EcN) with high biocompatibility and susceptibility to genetic modification is often applied in bacterial therapies for cancer. However, most studies have used plasmids as vectors to construct engineering strains from EcN. Plasmid-based expression systems suffer from genetic instability, and they need antibiotic selective pressure to maintain high copy number. This study aimed to employ EcN for synthesizing the photosensitizer 5-aminolevulinic acid (5-ALA). Firstly, the key genes of 5-ALA synthesis, hemA^M and hemL, were integrated into the EcN genome by the phage integration technique. Then, chemically inducible chromosomal evolution (CIChE) was adopted to increase the copy number of hemA^M and hemL and thus improved the stable synthesis of 5-ALA. The in vitro cell experiments verified that the constructed engineering strain can deliver stably synthesized 5-ALA to tumor cells and inhibit their growth. This study provided a basis for applying the engineering strains of EcN in the photodynamic therapy for tumors.
Escherichia coli/metabolism* ; Aminolevulinic Acid/metabolism* ; Photosensitizing Agents/pharmacology* ; Plasmids/genetics* ; Chromosomes, Bacterial/genetics* ; Genetic Engineering ; Humans ; Probiotics ; Photochemotherapy

OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; DNA Copy Number Variations ; Placenta ; Chromosomes, Human, Pair 1 ; In Situ Hybridization, Fluorescence ; Prenatal Diagnosis/methods* ; Fetus ; Amniotic Fluid ; Chromosome Aberrations ; Trisomy/genetics*

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Turner syndrome (TS) with rapidly progressive puberty. METHODS: A child who had presented at the Pediatric Endocrinology Clinic of the Shenzhen People's Hospital on January 19, 2022 was selected as the study subject. Clinical data of the child were collected. Peripheral blood sample of the child was subjected to chromosomal microarray analysis (CMA) and multiple ligation-dependent probe amplification (MLPA). Previous studies related to TS with rapidly progressive puberty were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases with Turner syndrome and rapidly progressive puberty as the keywords. The duration for literature retrieval was set from November 9, 2021 to May 31, 2022. The clinical characteristics and karyotypes of the children were summarized. RESULTS: The child was a 13-year-and-2-month-old female. She was found to have breast development at 9, short stature at 10, and menarche at 11. At 13, she was found to have a 46,X,i(X)(q10) karyotype. At the time of admission, she had a height of 143.5 cm (< P3), with 6 ~ 8 nevi over her face and right clavicle. She also had bilateral simian creases but no saddle nasal bridge, neck webbing, cubitus valgus, shield chest or widened breast distance. She had menstruated for over 2 years, and her bone age has reached 15.6 years. CMA revealed that she had a 58.06 Mb deletion in the Xp22.33p11.1 region and a 94.49 Mb duplication in the Xp11.1q28 region. MLPA has confirmed monosomy Xp and trisomy Xq. A total of 13 reports were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases, which had included 14 similar cases. Analysis of the 15 children suggested that their main clinical manifestations have included short stature and growth retardation, and their chromosomal karyotypes were mainly mosaicisms. CONCLUSION The main clinical manifestations of TS with rapidly progressive puberty are short stature and growth retardation. Deletion in the Xp22.33p11.1 and duplication in the Xp11.1q28 probably underlay the TS with rapid progression in this child, which has provided a reference for clinical diagnosis and genetic counselling for her.
Humans ; Female ; Adolescent ; Puberty ; Turner Syndrome/genetics* ; Chromosomes, Human, X ; Karyotyping

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Branchio-Oto syndrome (BOS). METHODS: A pedigree with BOS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples of the proband and her parents were collected. Whole exome sequencing (WES) was carried out for the proband. Multiplex ligation-dependent probe amplification (MLPA) was used to verify the result of WES, short tandem repeat (STR) analysis was used to verify the relationship between the proband and her parents, and the pathogenicity of the candidate variant was analyzed. RESULTS: The proband, a 6-year-old girl, had manifested severe congenital deafness, along with inner ear malformation and bilateral branchial fistulae. WES revealed that she has harbored a heterozygous deletion of 2 466 kb at chromosome 8q13.3, which encompassed the EYA1 gene. MLPA confirmed that all of the 18 exons of the EYA1 gene were lost, and neither of her parents has carried the same deletion variant. STR analysis supported that both of her parents are biological parents. Based on the guidelines from the American College of Medical Genetics and Genomics, the deletion was classified as pathogenic (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION The heterozygous deletion of EYA1 gene probably underlay the pathogenicity of BOS in the proband, which has provided a basis for the clinical diagnosis.
Humans ; Female ; Pregnancy ; Child ; Pedigree ; Family ; Parents ; Chromosomes, Human, Pair 3 ; Exons ; Nuclear Proteins/genetics* ; Protein Tyrosine Phosphatases ; Intracellular Signaling Peptides and Proteins/genetics*

OBJECTIVE: To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8. METHODS: Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness. RESULTS: The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3]. CONCLUSION The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
Female ; Pregnancy ; Humans ; Chromosomes, Human, Pair 8/genetics* ; In Situ Hybridization, Fluorescence ; Gene Rearrangement ; Prenatal Diagnosis ; Centromere

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins