OBJECTIVE: To investigate the genetic characteristics and clinical utility of Optical genome mapping (OGM) in resolving complex genomic rearrangements in families with recurrent pregnancy loss. METHODS: A recurrent miscarriage family which presented at both the People's Hospital of Qianxinan Buyi and Miao Autonomous Prefecture and the Affiliated Women and Children's Hospital of Ningbo University in September 2024 was selected as the study subject. Relevant clinical information was collected. Peripheral blood samples of the couple were collected for G banding karyotyping analysis, and copy number variation sequencing (CNV-seq) and OGM were used for verification. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2024-148). RESULTS: CNV-seq in an external hospital detected a 10.67 Mb deletion in the 16q12.1q21 region, a 142.4 kb deletion in the 5p15.2 region, and a 359.55 kb duplication in the 7p22.2 region. No abnormality was found in the chromosomal karyotype of the male partner, and the initial karyotyping of the female partner suggested 46,XX,?del(16)(q12.1q22). The CNV-seq verification of her indicated only variations in the 5p15.2 and 7p22.2 fragments, and no deletion of 16q was detected. As indicated by precise OGM analysis, multiple intrachromosomal and interchromosomal translocation variations had occurred between chromosomes 10 and 16 in the female partner, with complex balanced rearrangements (including 5 transchromosomal breakpoints). CONCLUSION The complex balanced rearrangements of the female partner's chromosomes had occurred during meiosis, the resultant unbalanced gametes may be the cause of repeated miscarriage in this family. OGM can delineate complex rearrangement breakpoints and directions that are difficult to reveal by conventional karyotyping analysis and provide a basis for accurate reproductive genetic counseling.
Humans ; Abortion, Habitual/etiology* ; Female ; Pregnancy ; Male ; DNA Copy Number Variations/genetics* ; Adult ; Karyotyping ; Pedigree ; Gene Rearrangement ; Chromosome Mapping

OBJECTIVE: To determine the carrier rate for thalassemia mutations in the ethnic Miao population of Qianxinan Prefecture. METHODS: Ethnic Miao people suspected for thalassemia trait at the People's Hospital of Qianxinan Prefecture, Guizhou Province between November 2020 to September 2024 were selected as the study subjects. Gap-PCR technology combined with high-throughput sequencing was used to screen a total of 666 individuals. ArcMap v10.8.2 was used to create a spatial distribution map of thalassemia based on the screening results. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2016-01). RESULTS: In total 254 positive cases were detected, with an overall positive rate of 38.14%. Among these, 173 cases were α-thalassemia (25.98%), 77 cases were β-thalassemia (11.56%), and 4 cases were αβ compound thalassemia (0.60%). The most common genotypes for α-thalassemia were αα/--^SEA (positive rate = 10.06%, accounting for 38.73%), αα/-α^3.7 (positive rate = 8.86%, accounting for 34.10%), and α^CSα/αα (positive rate = 4.95%, accounting for 19.08%). The most common genotypes for β-thalassemia were β^41/42(-TTCT)/β^A (positive rate = 5.11%, accounting for 44.16%) and β^{17 (A>T)}/β^A(positive rate = 4.20%, accounting for 36.36%), with these two genotypes accounting for as much as 80.52%. The spatial distribution map indicated that the highest overall detection rate of thalassemia and α-thalassemia in the Miao population of Qianxinan Prefecture was in Xingyi City. The highest detection rate of β-thalassemia was in Zhenfeng County, and the highest detection rate of αβ compound thalassemia was in Wangmo County. CONCLUSION The detection rate of thalassemia among the ethnic Miaos from Qianxinan Prefecture is relatively high, which primarily consisted of α-thalassemia. Regular monitoring and educational outreach should be conducted.
Humans ; China/ethnology* ; Female ; Male ; Genetic Testing ; Adult ; alpha-Thalassemia/genetics* ; Thalassemia/ethnology* ; Ethnicity/genetics* ; Genotype ; beta-Thalassemia/ethnology* ; Adolescent ; Mutation ; Middle Aged ; Child ; Asian People/genetics* ; Young Adult

Objective:To analyze the thalassemia screening and genotyping in Southwest Guizhou Autonomous Prefecture (referred it as Qianxinan Prefecture), this essay provides the theoretical reference for clinical diagnosis of thalassemia and suspicious cases.Methods:The pregnant women, spouses and neonates who were screened for thalassemia gene in Qian Xi Nan People's Hospital from January 2016 to December 2020 were selected as the research subjects, and peripheral blood or umbilical cord blood samples were collected to extract DNA. The gap-polymerase chain reaction (Gap-PCR) and next-generation sequencing (NGS) technology were used to screen thalassemia, and ArcMap 10.8 software was adopted to map the local spatial distribution of thalassemia based on the screening data.Results:A total of 67 185 cases of people from various regions in Qianxinan Prefecture were screened, and 8 202 cases of thalassemia gene carriers were detected, with a total detection rate of 12.21%. Among them, 5 660 cases of α-thalassemia, with a detection rate of 8.42%; 2 132 cases of β-thalassemia, with a detection rate of 3.17%; 410 cases of αβ complex thalassemia, with a detection rate of 0.61%. In the detection of thalassemia genes, 27 genotypes of α-thalassemia were detected, mainly αα/-α 3.7, accounting for 41.13% (2 328/5 660); 33 genotypes of β-thalassemia were detected, mainly β CD17(A>T)/β A, accounting for 44.09% (940/2 132); 55 genotypes of αβ complex thalassemia were detected, and αα/-α 3.7 complexed β CD17(A>T)/β A dominated, accounting for 21.22% (87/410). There were high incidence areas in the spatial distribution of thalassemia, which were Wangmo County and Ceheng County, and the detection rate was 26.76% (1 438/5 374), 24.39% (1 314/5 387), respectively. Conclusions:The detection rate of thalassemia gene in Qianxinan Prefecture is relatively high, mainly αα/-α 3.7 genotype of α-thalassemia. Wangmo County and Ceheng County are high-incidence areas of thalassemia, and screening efforts should be continued.