تقرير
The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.
| العنوان: | The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders. |
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| المؤلفون: | Yılmaz M; Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey., Kamaşak T; Department of Pediatric Neurology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey., Teralı K; Department of Medical Biochemistry, Faculty of Medicine, Cyprus International University, Nicosia, Cyprus., Çebi AH; Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey., Türkyılmaz A; Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. |
| المصدر: | American journal of medical genetics. Part A [Am J Med Genet A] 2024 May; Vol. 194 (5), pp. e63535. Date of Electronic Publication: 2024 Jan 08. |
| نوع المنشور: | Case Reports |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hoboken, N.J. : Wiley-Blackwell Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| مواضيع طبية MeSH: | Intellectual Disability*/genetics , Intellectual Disability*/diagnosis, Humans ; AlkB Homolog 8, tRNA Methyltransferase/genetics ; Developmental Disabilities/genetics ; Mutation, Missense/genetics ; Phenotype ; RNA, Transfer/genetics |
| مستخلص: | ABH8, the protein encoded by the ALKBH8 gene, modifies tRNAs by methylating their anticodon wobble uridine residues. The variations in the ALKBH8 gene are associated with the "intellectual developmental disorder, autosomal recessive type 71" (MIM: 618504) phenotype in the OMIM database. This phenotype is characterized by global developmental delay, facial dysmorphic features, and psychiatric problems. To date, 12 patients from five distinct families carrying variants of the ALKBH8 gene have been reported in the literature. In the present study, we report the first Turkish family harboring a novel homozygous missense variant, NM_138775.3:c.1874G > C (p.Arg625Pro), in the last exon of the ALKBH8 gene. Two affected siblings in this family showed signs of global developmental delay and intellectual disability. Based on the dysmorphological assessment of the cases, fifth finger clinodactyly and fetal fingertip pads were prominent, in addition to the dysmorphic findings similar to those reported in previous studies. Minor dysmorphic limb anomalies in relation to this phenotype have not yet been previously reported in the literature. Our computational studies revealed the potential deleterious effects of the Arg-to-Pro substitution on the structure and stability of the ABH8 methyltransferase domain. In the present report, the first Turkish family with an ultrarare disease associated with the ALKBH8 gene was reported, and a novel deleterious variant in the ALKBH8 gene and additional clinical features that were not reported with this condition have been reported. (© 2024 Wiley Periodicals LLC.) |
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| فهرسة مساهمة: | Keywords: ABH8; ALKBH8; exome sequencing; intellectual disability; tRNA modification |
| المشرفين على المادة: | EC 1.14.11.- (AlkB Homolog 8, tRNA Methyltransferase) EC 1.14.11.- (ALKBH8 protein, human) 9014-25-9 (RNA, Transfer) |
| تواريخ الأحداث: | Date Created: 20240108 Date Completed: 20240411 Latest Revision: 20240812 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1002/ajmg.a.63535 |
| PMID: | 38189198 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1552-4833 |
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| DOI: | 10.1002/ajmg.a.63535 |