Expanding the clinical and genetic heterogeneity of SPAX5

Abstract

Mutations in the ATPase family 3-like gene (AFG3L2) have been linked to autosomal-dominant spinocerebellar ataxia type 28 and autosomal recessive spastic ataxia-neuropathy syndrome. Here, we describe the case of a child carrying bi-allelic mutations in AFG3L2 and presenting with ictal paroxysmal episodes associated with neuroimaging suggestive of basal ganglia involvement. Studies in skin fibroblasts showed a significant reduction of AFG3L2 expression. The relatively mild clinical presentation and the benign course, in spite of severe neuroimaging features, distinguish this case from data reported in the literature, and therefore expand the spectrum of neurological and neuroradiological features associated with AFG3L2 mutations.

Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

“…Prior to this study, all patients had been tested for pathological trinucleotide repeat expansions associated with FRDA and SCA1, 2, 3, 6, 7, 17 and FMR1. Exome sequencing in families I and J (trio analysis) was performed as described previously [8]. The patients were evaluated by SARA (Scale for the Assessment and Rating of Ataxia), that ranges from 0 (no ataxia) to 40 (severe ataxia) [10], and by disability scale SDFS (Spinocerebellar Degeneration Functional Score), that spans from 0 (no disability) to 7 (bedridden) [11].…”

“…This study was approved by Local Ethics Committees. All the participants (or their legal guardians in case of children) provided written informed consent, according to Italian National Health System guidelines and Declaration of Helsinki, to participate to the study as described before [ 8 ]. Briefly, a TRP (SureSelect, Agilent, Santa Clara, CA) encompassing 273 genes related to inherited ataxias was employed, and sequencing was carried out using a NextSeq 500 (Illumina, San Diego, CA) platform (see Supplementary Table 1).…”

“…Prior to this study, all patients had been tested for pathological trinucleotide repeat expansions associated with FRDA and SCA1, 2, 3, 6, 7, 17 and FMR1 . Exome sequencing in families I and J (trio analysis) was performed as described previously [ 8 ].…”

Multimodal evaluation of an Italian family with a hereditary spastic paraplegia and POLR3A mutations

“…Genomic DNA was purified from blood sample using the standard phenol extraction protocol. The NGS study was performed as described by Dosi et al 13 using a customized bioinformatic pipeline 14 to confirm the impact of mutations in silico according to ACMG guidelines 15 …”

Levodopa Responsive Dystonia Parkinsonism, Intellectual Disability, and Optic Atrophy Due to a Heterozygous Missense Variant in AFG3L2

“…AFG3L2 mutations are associated with several neurodegenerative disorders. 1 , 2 , 3 , 4 , 5 The ATP‐dependent mitochondrial AAA+ metalloprotease ( m ‐AAA) has 2 subunits: AFG3L2 and paraplegin. AFG3L2 is encoded by the gene AFG3L2 and paraplegin is encoded by the gene, SPG7 .…”