Neurodevelopmental disorder in an Egyptian family with a biallelic ALKBH8 variant
© 2021 Wiley Periodicals LLC..
Alkylated DNA repair protein AlkB homolog 8 (ALKBH8) is a member of the AlkB family of dioxygenases. ALKBH8 is a methyltransferase of the highly variable wobble nucleoside position in the anticodon loop of tRNA and thus plays a critical role in tRNA modification by preserving codon recognition and preventing errors in amino acid incorporation during translation. Moreover, its activity catalyzes uridine modifications that are proposed to be critical for accurate protein translation. Previously, two distinct homozygous truncating variants in the final exon of ALKBH8 were described in two unrelated large Saudi Arabian kindreds with intellectual developmental disorder and autosomal recessive 71 (MRT71) syndrome (MIM# 618504). Here, we report a third family-of Egyptian descent-harboring a novel homozygous frame-shift variant in the last exon of ALKBH8. Two affected siblings in this family exhibit global developmental delay and intellectual disability as shared characteristic features of MRT71 syndrome, and we further characterize their observed dysmorphic features and brain MRI findings. This description of a third family with a truncating ALKBH8 variant from a distinct population broadens the phenotypic and genotypic spectrum of MRT71 syndrome, affirms that perturbations in tRNA biogenesis can contribute to neurogenetic disease traits, and firmly establishes ALKBH8 as a novel neurodevelopmental disease gene.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:185 |
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| Enthalten in: |
American journal of medical genetics. Part A - 185(2021), 4 vom: 01. Apr., Seite 1288-1293 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saad, Ahmed K [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.08.2021 Date Revised 21.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ajmg.a.62100 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321055276 |
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| 100 | 1 | |a Saad, Ahmed K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Neurodevelopmental disorder in an Egyptian family with a biallelic ALKBH8 variant |
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| 500 | |a Date Revised 21.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Wiley Periodicals LLC. | ||
| 520 | |a Alkylated DNA repair protein AlkB homolog 8 (ALKBH8) is a member of the AlkB family of dioxygenases. ALKBH8 is a methyltransferase of the highly variable wobble nucleoside position in the anticodon loop of tRNA and thus plays a critical role in tRNA modification by preserving codon recognition and preventing errors in amino acid incorporation during translation. Moreover, its activity catalyzes uridine modifications that are proposed to be critical for accurate protein translation. Previously, two distinct homozygous truncating variants in the final exon of ALKBH8 were described in two unrelated large Saudi Arabian kindreds with intellectual developmental disorder and autosomal recessive 71 (MRT71) syndrome (MIM# 618504). Here, we report a third family-of Egyptian descent-harboring a novel homozygous frame-shift variant in the last exon of ALKBH8. Two affected siblings in this family exhibit global developmental delay and intellectual disability as shared characteristic features of MRT71 syndrome, and we further characterize their observed dysmorphic features and brain MRI findings. This description of a third family with a truncating ALKBH8 variant from a distinct population broadens the phenotypic and genotypic spectrum of MRT71 syndrome, affirms that perturbations in tRNA biogenesis can contribute to neurogenetic disease traits, and firmly establishes ALKBH8 as a novel neurodevelopmental disease gene | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a ALKBH8 | |
| 650 | 4 | |a intellectual disability | |
| 650 | 4 | |a neurodevelopmental delay | |
| 650 | 4 | |a tRNA modification | |
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| 700 | 1 | |a Marafi, Dana |e verfasserin |4 aut | |
| 700 | 1 | |a Mitani, Tadahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Haowei |e verfasserin |4 aut | |
| 700 | 1 | |a Rafat, Karima |e verfasserin |4 aut | |
| 700 | 1 | |a Fatih, Jawid M |e verfasserin |4 aut | |
| 700 | 1 | |a Jhangiani, Shalini N |e verfasserin |4 aut | |
| 700 | 1 | |a Coban-Akdemir, Zeynep |e verfasserin |4 aut | |
| 700 | 0 | |a Baylor-Hopkins Center for Mendelian Genomics |e verfasserin |4 aut | |
| 700 | 1 | |a Gibbs, Richard A |e verfasserin |4 aut | |
| 700 | 1 | |a Pehlivan, Davut |e verfasserin |4 aut | |
| 700 | 1 | |a Hunter, Jill V |e verfasserin |4 aut | |
| 700 | 1 | |a Posey, Jennifer E |e verfasserin |4 aut | |
| 700 | 1 | |a Zaki, Maha S |e verfasserin |4 aut | |
| 700 | 1 | |a Lupski, James R |e verfasserin |4 aut | |
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