Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Schaflinger, E; Blatterer, J; Khan, AS; Kaufmann, L; Auinger, L; Tatrai, B; Abbasi, SW; Zeeshan, Ali, M; Abbasi, AA; Al, Kaissi, A; Petek, E; Wagner, K; Ahmad, Khan, M; Windpassinger, C.
An exceptional biallelic N-terminal frame shift mutation in ZMPSTE24 leads to non-lethal progeria due to possible utilization of a downstream alternative start codon.
Gene. 2022; 833: 146582
Doi: 10.1016/j.gene.2022.146582
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Blatterer Jasmin
- Windpassinger Christian
- Co-authors Med Uni Graz
- Auinger Lisa
- Kaufmann Lukas
- Petek Erwin
- Wagner Klaus
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- Abstract:
- Biallelic mutations in ZMPSTE24 are known to be associated with autosomal recessive mandibuloacral dysplasia with type B lipodystrophy (MADB) and lethal restrictive dermopathy (RD), respectively. Disease manifestation is depending on the remaining enzyme activity of the mutated ZMPSTE24 protein. To date, complete loss of function has exclusively been reported in RD cases. In this study, we identified a novel N-terminal homozygous frameshift mutation (c.28_29insA) in a consanguineous family segregating with MADB. An in-depth analysis of the mutated sequence revealed, that the one base pair insertion creates a novel downstream in-frame start codon, which supposedly serves as an alternative translation initiation site (TIS). This possible rescue mechanism would explain the relatively mild clinical outcome in the studied individuals. Our findings demonstrate the necessity for careful interpretation of N-terminal variants potentially effecting translation initiation.
- Find related publications in this database (using NLM MeSH Indexing)
- Codon, Initiator - genetics
- Frameshift Mutation - administration & dosage
- Humans - administration & dosage
- Lamin Type A - genetics, metabolism
- Lipodystrophy - genetics
- Membrane Proteins - genetics, metabolism
- Metalloendopeptidases - genetics
- Mutation - administration & dosage
- Progeria - genetics
- Find related publications in this database (Keywords)
- ZMPSTE24
- Translation initiation
- Alternative start codon
- Lethal restrictive dermopathy
- Mandibuloacral dysplasia