Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing
Abstract To explore the genetic cause of a four-generation severe intellectual disability in a Chinese family using nanopore sequencing and to provide genetic counseling and reproductive guidance for family members. Multiple genetic analyses of the proband and family members were performed, includin...
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Nature Portfolio
2025-01-01
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| author | Xingwu Wu Qiang Xu Ge Chen Jialyv Huang Yanying Zhong Lifeng Tian Qiongfang Wu Jia Chen |
| author_facet | Xingwu Wu Qiang Xu Ge Chen Jialyv Huang Yanying Zhong Lifeng Tian Qiongfang Wu Jia Chen |
| author_sort | Xingwu Wu |
| collection | DOAJ |
| description | Abstract To explore the genetic cause of a four-generation severe intellectual disability in a Chinese family using nanopore sequencing and to provide genetic counseling and reproductive guidance for family members. Multiple genetic analyses of the proband and family members were performed, including chromosome karyotype analysis, whole exome sequencing, nanopore sequencing, PCR amplification, and Sanger sequencing. The results of G-binding karyotyping, CGG repeats for FMR1, GGC repeats for NOTCH2NCL, and trio-whole-exome sequencing were negative for the proband and his parents. Nanopore sequencing showed that the proband carried 12q24.33 microduplication (3.26 Mb) and 22q13.33 microdeletion (1.5 Mb). According to the guidelines of the American Society for Medical Genetics and Genomics (ACMG), the 22q13.33 microdeletion was classified as pathogenic, whereas the 12q24.33 microduplication was classified as a variant of uncertain significance (VUS). The precise karyotype and location of chromosomal breakpoints in the patient and family members were determined through PCR. According to the results of Sanger sequencing, a cryptic balanced translocation was detected in the proband’s father. Additionally, informative SNPs were identified near the breakpoints for preimplantation genetic testing for structure rearrangement (PGT-SR) treatment by nanopore sequencing. We identified a cryptic unbalanced translocation in a large Chinese family with Phelan-McDermid syndrome (22q13.33 deletion syndrome) by nanopore sequencing. Nanopore sequencing can be a powerful tool for the genetic diagnosis of unexplained intellectual disability and the detection of precise breakpoints of chromosomal rearrangement in PGT-SR treatment. |
| format | Article |
| id | doaj-art-331d3d1a3a4745c284e8a94296243bf8 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-331d3d1a3a4745c284e8a94296243bf82025-01-26T12:26:51ZengNature PortfolioScientific Reports2045-23222025-01-011511810.1038/s41598-025-87083-8Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencingXingwu Wu0Qiang Xu1Ge Chen2Jialyv Huang3Yanying Zhong4Lifeng Tian5Qiongfang Wu6Jia Chen7Reproductive Medicine Center, Jiangxi Maternal and Child Health HospitalReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalJiangxi Key Laboratory of Reproductive Health, Jiangxi Maternal and Child Health HospitalReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang UniversityReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalAbstract To explore the genetic cause of a four-generation severe intellectual disability in a Chinese family using nanopore sequencing and to provide genetic counseling and reproductive guidance for family members. Multiple genetic analyses of the proband and family members were performed, including chromosome karyotype analysis, whole exome sequencing, nanopore sequencing, PCR amplification, and Sanger sequencing. The results of G-binding karyotyping, CGG repeats for FMR1, GGC repeats for NOTCH2NCL, and trio-whole-exome sequencing were negative for the proband and his parents. Nanopore sequencing showed that the proband carried 12q24.33 microduplication (3.26 Mb) and 22q13.33 microdeletion (1.5 Mb). According to the guidelines of the American Society for Medical Genetics and Genomics (ACMG), the 22q13.33 microdeletion was classified as pathogenic, whereas the 12q24.33 microduplication was classified as a variant of uncertain significance (VUS). The precise karyotype and location of chromosomal breakpoints in the patient and family members were determined through PCR. According to the results of Sanger sequencing, a cryptic balanced translocation was detected in the proband’s father. Additionally, informative SNPs were identified near the breakpoints for preimplantation genetic testing for structure rearrangement (PGT-SR) treatment by nanopore sequencing. We identified a cryptic unbalanced translocation in a large Chinese family with Phelan-McDermid syndrome (22q13.33 deletion syndrome) by nanopore sequencing. Nanopore sequencing can be a powerful tool for the genetic diagnosis of unexplained intellectual disability and the detection of precise breakpoints of chromosomal rearrangement in PGT-SR treatment.https://doi.org/10.1038/s41598-025-87083-8Phelan-McDermid syndromeNanopore sequencingCryptic balanced translocation22q13.33 deletion |
| spellingShingle | Xingwu Wu Qiang Xu Ge Chen Jialyv Huang Yanying Zhong Lifeng Tian Qiongfang Wu Jia Chen Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing Scientific Reports Phelan-McDermid syndrome Nanopore sequencing Cryptic balanced translocation 22q13.33 deletion |
| title | Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing |
| title_full | Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing |
| title_fullStr | Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing |
| title_full_unstemmed | Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing |
| title_short | Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing |
| title_sort | identification of a cryptic unbalanced translocation der 22 t 12 22 q24 33 q13 33 in a large chinese family with phelan mcdermid syndrome by nanopore sequencing |
| topic | Phelan-McDermid syndrome Nanopore sequencing Cryptic balanced translocation 22q13.33 deletion |
| url | https://doi.org/10.1038/s41598-025-87083-8 |
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