Case Report: Two Families With Related Neurodegeneration

Overview

Journal Front Genet

Date 2022 Feb 28

PMID 35222531

Authors

Ieva Micule

Baiba Lace

Nathan T Wright

Nicolas Chrestian

Jurgis Strautmanis

Mikus Diriks

Janis Stavusis

Dita Kidere

Elfa Kleina

Anna Zdanovica

Nataly Laflamme

Nadie Rioux

Samarth Thonta Setty

Sander Pajusalu

Arnaud Droit

Monkol Lek

Serge Rivest

Inna Inashkina

Affiliations

Soon will be listed here.

Abstract

There are recent reports of associations of variants in the 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 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 mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.

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