Disease relevance of fer-1

• A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B [1].

High impact information on fer-1

• This gene shows no homology to any known mammalian gene, but its predicted product is related to the C. elegans spermatogenesis factor fer-1 [1].
• Dysferlin is a homologue of the Caenorhabditis elegans fer-1 gene, which mediates vesicle fusion to the plasma membrane in spermatids [2].
• In fer-1 mutant males, spermatids appear normal, but during spermiogenesis membranous organelles (MO) fail to fuse with the sperm plasma membrane and a short, though motile. pseudopod is formed [3].
• Dysferlin, the gene product of the limb girdle muscular dystrophy (LGMD) 2B locus, encodes a membrane-associated protein with homology to Caenorhabditis elegans fer-1 [4].
• To investigate its role in membranous organelle fusion, we examined ten fer-1 mutations and found that they all cause the same defect in membrane fusion [5].

Biological context of fer-1

• We identified the mutations associated with five fer-1 alleles, all of which are missense mutations causing single amino acid changes [6].

Anatomical context of fer-1

• Mutations in the gene fer-1 cause abnormal spermatozoa in which the MOs do not fuse, although they abut the plasma membrane normally [6].
• Here we describe the fer-1 gene, which we found to be approximately 8.6 kb in length and to encode a 6.2 kb transcript whose expression is limited to the primary spermatocytes, the cells in which the MOs form. fer-1 is predicted to encode a 235 kDa protein which is highly charged except for a putative transmembrane domain near the C terminus [6].

Associations of fer-1 with chemical compounds

• Most of the fer-1 mutations fall within these C2 domains, showing that they have distinct, non-redundant functions [5].

References