TY - JOUR
T1 - Congenital coenzyme Q5-linked pathology
T2 - causal genetic association, core phenotype, and molecular mechanism
AU - Dawidziuk, Mateusz
AU - Podwysocka, Aleksandra
AU - Jurek, Marta
AU - Obersztyn, Ewa
AU - Bekiesinska-Figatowska, Monika
AU - Goszczanska-Ciuchta, Alicja
AU - Bukowska-Olech, Ewelina
AU - Rygiel, Agnieszka Magdalena
AU - Guilbride, Dorothy Lys
AU - Wiszniewski, Wojciech
AU - Gawlinski, Pawel
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - COQ10
KW - COQ5
KW - Expansion of the phenotype
KW - Molecular mechanism
UR - http://www.scopus.com/inward/record.url?scp=85168396038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85168396038&partnerID=8YFLogxK
U2 - 10.1007/s13353-023-00773-9
DO - 10.1007/s13353-023-00773-9
M3 - Article
C2 - 37599337
AN - SCOPUS:85168396038
SN - 1234-1983
VL - 64
SP - 507
EP - 514
JO - Journal of Applied Genetics
JF - Journal of Applied Genetics
IS - 3
ER -