This report describes centronuclear myopathy 2 (CNM2), which is a subtype of centronuclear myopathy; CNM2 exhibits autosomal recessive inheritance. The human gene implicated in this disease is BIN1, which encodes a nucleocytoplasmic adaptor protein involved in membrane sensing/remodeling and intracellular membrane trafficking. There is a single orthologous gene in Drosophila, Amph, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated. Dmel\Amph is also orthologous to the human genes AMPH and BIN2.
The human Hsap\BIN1 gene has been introduced into flies, but has not been used in the context of this disease model.
Animals homozygous for loss-of-function mutation of Dmel\Amph exhibit locomotor and larval muscle defects; at the cellular level, defects in positioning of nuclei within larval muscle cells (which are multinucleate) are observed. Loss-of-function muscle phenotypes of Drosophila genes related to human genes associated with EDMD vs. genes associated centronuclear myopathy have been compared (see 'Emery-Dreifuss muscular dystrophy, LINC-complex-related' FBhh0000812 and 'centronuclear myopathy, X-linked' FBhh0000394). Physical and genetic interactions of Amph have been described; see below and in the Amph gene report.
[updated Jan. 2022 by FlyBase; FBrf0222196]
Centronuclear myopathy is a congenital myopathy characterized by slowly progressive muscular weakness and wasting; the disorder involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles; ptosis (drooping eyelid) and limitation of eye movements may occur. Age of onset varies, from childhood to young adulthood. (Bitoun et al., 2005, pubmed:16227997). [from MIM:160150; 2015.12.16]
[MYOPATHY, CENTRONUCLEAR, 2; CNM2](https://omim.org/entry/255200)
[BRIDGING INTEGRATOR 1; BIN1](https://omim.org/entry/601248)
Centronuclear myopathy-2 (CNM2) is caused by homozygous mutation in the amphiphysin-2 gene (BIN1). [from MIM:255200; 2018.05.24]
Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling and is involved in intracellular membrane trafficking in different cell types (Bohm, et al., 2013; pubmed:23754947).
BIN1 encodes several isoforms of a nucleocytoplasmic adaptor protein. Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynamin, synaptojanin, endophilin, and clathrin. Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process. [Gene Cards, BIN1; 2018.05.24]
Many to one (3 human to 1 Drosophila); the human genes are AMPH, BIN1, and BIN2.
Moderate-scoring ortholog of human AMPH, BIN1, and BIN2 (1 Drosophila to 3 human). Dmel\Amph shares 28-30% identity and 43-46% similarity with the human genes.
