@article{73b39dc08676459ba34f533d31febe5f,
title = "Case Report: Two Families With HPDL Related Neurodegeneration",
abstract = "There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.",
keywords = "ataxia, brain diseases, citrate-synthase, mitochondrial diseases, spastic paraplegia",
author = "Ieva Micule and Baiba Lace and Wright, {Nathan T} and Nicolas Chrestian and Jurgis Strautmanis and Mikus Diriks and Janis Stavusis and Dita Kidere and Elfa Kleina and Anna Zdanovica and Nataly Laflamme and Nadie Rioux and Setty, {Samarth Thonta} and Sander Pajusalu and Arnaud Droit and Monkol Lek and Serge Rivest and Inna Inashkina",
note = "Funding Information: La Fondation Marcelle et Jean Coutu, Fondation du CHU de Qu{\'e}bec and Fondation des {\'E}toiles (Qu{\'e}bec); Latvian Council of Science grant No: lzp-2018/1-0180 “The characterization and analysis of mitochondrial DNA mutations and variants of unknown significance using transmitochondrial cytoplasmic hybrid cell models”; Estonian Research Council grants MOBTP175 and PUTJD827; NSF (MCB-2024182) and the Dreyfus Foundation. Funding Information: La Fondation Marcelle et Jean Coutu, Fondation du CHU de Qu?bec and Fondation des ?toiles (Qu?bec); Latvian Council of Science grant No: lzp-2018/1-0180 ?The characterization and analysis of mitochondrial DNA mutations and variants of unknown significance using transmitochondrial cytoplasmic hybrid cell models?; Estonian Research Council grants MOBTP175 and PUTJD827; NSF (MCB-2024182) and the Dreyfus Foundation. Publisher Copyright: Copyright {\textcopyright} 2022 Micule, Lace, Wright, Chrestian, Strautmanis, Diriks, Stavusis, Kidere, Kleina, Zdanovica, Laflamme, Rioux, Setty, Pajusalu, Droit, Lek, Rivest and Inashkina.",
year = "2022",
doi = "10.3389/fgene.2022.780764",
language = "English",
volume = "13",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media SA",
number = "780764",
}