This report describes spastic paraplegia 76 (SPG76), which is a subtype of spastic paraplegia; SPG76 is inherited as an autosomal recessive. The human gene implicated in this disease is calpain 1 (CAPN1) which encodes one of many calpains (calcium-activated proteases) in humans. There are two Drosophila orthologs, CalpB and CalpA, for which classical amorphic alleles, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human CAPN1 gene has not been introduced into flies.
Neither CalpB nor CalpA is an essential gene in flies: animals homozygous for amorphic mutations of either are viable and fertile. CalpB is implicated in normal cell migration. Neuronal knockdown of CalpB effected by RNAi results in progressive locomotor defects. CalpA appears to play a role in myoblast fusion. Overexpression of CalpA in muscle cell progenitors results in partial embryonic lethality; overexpression in transverse muscles allows survival to larval stages, but results in impaired locomotor behavior. Several physical and genetic interactions for both fly genes have been reported; see below and in the gene reports for CalpB and CalpA.
[updated Mar. 2017 by FlyBase; FBrf0222196]
The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from OMIM:182600; 15.06.29]
[SPASTIC PARAPLEGIA 76, AUTOSOMAL RECESSIVE; SPG76](https://omim.org/entry/616907)
[CALPAIN 1; CAPN1](https://omim.org/entry/114220)
See general description of spastic paraplegia above. SPG76 is characterized by young-adult onset of slowly progressive spasticity of the lower limbs resulting in gait difficulties. Most affected individuals have upper limb involvement and additional features such as foot deformities and dysarthria. [from OMIM:616907; 2017.03.03]
The calpains, calcium-activated neutral proteases, are non-lysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. CAPN1 encodes the large subunit of the ubiquitous enzyme, calpain 1. [Gene Cards; CAPN1; 2017.03.03]
High- to moderate-scoring ortholog of human CAPN9, CAPN2, CAPN1, CAPN3, CAPN8, and others (2 Drosophila to multiple human). CalpB shares 44-45% identity and 62-64% similarity with CAPN9, CAPN2, and CAPN1.
High- to moderate-scoring ortholog of human CAPN9, CAPN8, CAPN2, CAPN1, CAPN3, and others (2 Drosophila to multiple human). CalpA shares 41-44% identity and 57-60% similarity with CAPN9, CAPN8, CAPN2, and CAPN1.