دورية أكاديمية
أعرض في EDS

Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.

التفاصيل البيبلوغرافية
العنوان: Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.
المؤلفون: Li G; Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Road, Shanghai, 200030, China.; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China., Chen Y; Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Road, Shanghai, 200030, China.; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China., Han X; Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Road, Shanghai, 200030, China.; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China., Li N; Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Road, Shanghai, 200030, China. liniu0509@163.com.; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China. liniu0509@163.com.; Faculty of Medical Laboratory Science, College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. liniu0509@163.com., Li S; Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Road, Shanghai, 200030, China. shuyuanli816@163.com.; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China. shuyuanli816@163.com.; Faculty of Medical Laboratory Science, College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. shuyuanli816@163.com.
المصدر: BMC pregnancy and childbirth [BMC Pregnancy Childbirth] 2024 Jul 01; Vol. 24 (1), pp. 456. Date of Electronic Publication: 2024 Jul 01.
نوع المنشور: Journal Article; Case Reports
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100967799 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2393 (Electronic) Linking ISSN: 14712393 NLM ISO Abbreviation: BMC Pregnancy Childbirth Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مواضيع طبية MeSH: T-Box Domain Proteins*/genetics , Chromosomes, Human, Pair 17*/genetics , Haplotypes* , Heterozygote*, Humans ; Female ; Pregnancy ; Adult ; Chromosome Deletion ; Exome Sequencing ; Sequence Deletion ; Fetus/abnormalities ; Ultrasonography, Prenatal
مستخلص: Background: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance.
Methods: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6.
Results: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman.
Conclusions: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 22Y11906700 Shanghai Science and Technology Innovation Action Plan
فهرسة مساهمة: Keywords: 17q12 microdeletion; Congenital scoliosis; Functional study; Novel variant; TBX6
المشرفين على المادة: 0 (T-Box Domain Proteins)
0 (TBX6 protein, human)
تواريخ الأحداث: Date Created: 20240702 Date Completed: 20240702 Latest Revision: 20240724
رمز التحديث: 20240725
مُعرف محوري في PubMed: PMC11218386
DOI: 10.1186/s12884-024-06653-2
PMID: 38951757
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2393
DOI:10.1186/s12884-024-06653-2