Congenital coenzyme Q5-linked pathology: causal genetic association, core phenotype, and molecular mechanism

Coenzyme Q5 ( COQ5 ), a C-methyltransferase, modifies coenzyme Q10 (COQ10) during biosynthesis and interacts with polyA-tail regulating zinc-finger protein ZC3H14 in neural development. Here, we present a fifth patient (a third family) worldwide with neurodevelopmental and physiological symptoms inc...

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Published in:Journal of applied genetics 2023-09, Vol.64 (3), p.507-514
Main Authors: Dawidziuk, Mateusz, Podwysocka, Aleksandra, Jurek, Marta, Obersztyn, Ewa, Bekiesinska-Figatowska, Monika, Goszczanska-Ciuchta, Alicja, Bukowska-Olech, Ewelina, Rygiel, Agnieszka Magdalena, Guilbride, Dorothy Lys, Wiszniewski, Wojciech, Gawlinski, Pawel
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Ataxia
Atrophy
Biomedical and Life Sciences
Biosynthesis
Cerebellar ataxia
Cerebellum
Coenzyme Q10
Comparative analysis
Encephalopathy
Enzymes
Genetic aspects
Genetic disorders
Human Genetics
Human Genetics • Short Communication
Intellectual disabilities
Life Sciences
Methyltransferase
Microbial Genetics and Genomics
Molecular modelling
mRNA
Pathology
Phenotypes
Physiological aspects
Plant Genetics and Genomics
Zinc finger proteins
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Summary:Coenzyme Q5 ( COQ5 ), a C-methyltransferase, modifies coenzyme Q10 (COQ10) during biosynthesis and interacts with polyA-tail regulating zinc-finger protein ZC3H14 in neural development. Here, we present a fifth patient (a third family) worldwide with neurodevelopmental and physiological symptoms including COQ10 deficiency. Our patient harbors one novel c.681+1G>A and one recurrent p.Gly118Ser variant within COQ5 . The patient’s mRNA profile reveals multiple COQ5 splice-variants. Subsequently, we comprehensively described patient’s clinical features as compared to phenotype and symptoms of other known congenital coenzyme Q5-linked cases. A core spectrum of COQ5 -associated symptoms includes reduced COQ10 levels, intellectual disability, encephalopathy, cerebellar ataxia, cerebellar atrophy speech regression/dysarthria, short stature, and developmental delays. Our patient additionally displays dysmorphia, microcephaly, and regressive social faculties. These results formally establish causal association of biallelic COQ5 mutation with pathology, outline a core COQ5 -linked phenotype, and identify mRNA mis-splicing as the molecular mechanism underlying all COQ5 variant-linked pathology to date.
ISSN:1234-1983
2190-3883
DOI:10.1007/s13353-023-00773-9