This report describes spinal muscular atrophy, Jokela type (SMAJ), which is a subtype of spinal muscular atrophy. SMAJ exhibits autosomal dominant inheritance. The gene implicated in this disease is CHCHD10, which encodes a small mitochondrial protein that may be involved in the maintenance of mitochondrial organization and mitochondrial cristae structure. The Drosophila gene most closely related to CHCHD10 is Chchd2, for which loss-of-function mutations, RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated. There are two additional moderate-scoring orthologs in flies, CG31007 and CG31008, and there is a second similar gene in human, CHCHD2.
A UAS construct of the wild-type human Hsap\CHCHD10 gene has been introduced into flies, but has not been characterized.
A variant implicated in SMAJ has been characterized in flies, using the fly gene with the analogous change. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G88V in the fly Chchd2 gene (corresponds to G66V in the human CHCHD10 gene). A CHCHD10 variant implicated in a similar disease has also been characterized in this system; see ‘frontotemporal dementia and/or amyotrophic lateral sclerosis 2’ (FBhh0001227).
In Drosophila, loss of Dmel\Chchd2 function results in mitochondrial and neuronal phenotypes including increased sensitivity to oxidative stress, progressive dopaminergic neuron loss, progressive degeneration of photoreceptor cells, and progressive locomotor dysfunction. In fat body cells, loss of Chchd2 results in fragmented mitochondria. Genetic interactions have been described for Dmel\Chchd2; see the Chchd2 gene report.
[updated Jul. 2020 by FlyBase; FBrf0222196]
Spinal muscular atrophy (SMA) is characterized by progressive muscle weakness resulting from degeneration and loss of the anterior horn cells (i.e., lower motor neurons) in the spinal cord and the brain stem nuclei. Onset ranges from before birth to adolescence or young adulthood. Poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint contractures are common complications. [From GeneReviews, Spinal Muscular Atrophy, pubmed:20301526 2016.07.11]
[SPINAL MUSCULAR ATROPHY, JOKELA TYPE; SMAJ](https://omim.org/entry/615048)
[COILED-COIL-HELIX-COILED-COIL-HELIX DOMAIN-CONTAINING PROTEIN 10; CHCHD10](https://omim.org/entry/615903)
The Jokela type of spinal muscular atrophy (SMAJ) is an autosomal dominant lower motor neuron disorder characterized by adult-onset of muscle cramps and fasciculations affecting the proximal and distal muscles of the upper and lower limbs. The disorder is slowly progressive, resulting in weakness and mild muscle atrophy later in life (summary by Jokela et al., 2011; pubmed:21715705). [from MIM:615048; 2020.07.25]
The Jokela type of spinal muscular atrophy (SMAJ) is caused by heterozygous mutation in the CHCHD10 gene. [from MIM:615048; 2020.07.25]
CHCHD10 is a relatively small protein of the mitochondrial intermembrane space that is enriched at cristae junctions. It is predicted to be involved in oxidative phosphorylation or in maintenance of cristae morphology (Bannwarth et al., 2014; pubmed:24934289). [from MIM:615903; 2020.07.25]
High-scoring ortholog of human CHCHD2 and CHCH10 (3 Drosophila to 2 human). Dmel\Chchd2 shares 44-50% identity and 54-58% similarity with the human genes.
