This report describes Charcot-Marie-Tooth disease, type 4B1, an autosomal recessive subtype of Charcot-Marie-Tooth disease. The human gene implicated is MTMR2, which encodes Myotubularin Related Protein 2, a member of the myotubularin family of phosphoinositide lipid phosphatases. There is one high-scoring fly ortholog, Dmel\mtm, for which amorphic or loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human gene Hsap\MTMR2 have been introduced into flies, including both the wild-type gene and a disease-implicated variant, G103E. See the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) of some aspects of the null Dmel\mtm phenotype by expression of wild-type, but not mutant, Hsap\MTMR2 has been demonstrated
Loss-of-function mutations of mtm result in a tissue overgrowth phenotype.
[updated Apr. 2024 by FlyBase; FBrf0222196]
Charcot-Marie-Tooth disease (CMT) constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. CMT is divided into several major types: Type 1 is characterized by demyelination and by a significantly slowed motor median nerve conduction velocity (NCV). Type 2 is characterized by axonal abnormalities and a normal or slightly reduced NCV. "Intermediate" types describe CMT families with nerve conduction velocities, in different affected individuals, that overlap the division between Type 1 and Type 2. Additional types are defined on the basis inheritance patterns. [from MIM:609260 and MIM:606482; 2015.12.15]
Symptoms typically include progressive distal muscle weakness and atrophy, often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet. [from Gene Reviews, http://www.ncbi.nlm.nih.gov/books/NBK1358 2015.12.15]
[CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4B1; CMT4B1](https://omim.org/entry/601382)
[MYOTUBULARIN-RELATED PROTEIN 2; MTMR2](https://omim.org/entry/603557)
Charcot-Marie-Tooth disease type 4B1 (CMT4B1) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by an early childhood-onset of severe, demyelinating sensorimotor neuropathy, various degrees of complex myelin outfoldings seen on peripheral nerve biopsy, very slow, and often undetectable, nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and frequent pes cavus). Other reported features include facial weakness, vocal cord paresis, respiratory difficulties, and skeletal deformities (e.g. chest deformities, claw hands, pes equinovarus). [from orpha.net orpha:99955 ; 2022.12.21]
Charcot-Marie-Tooth disease type 4B1 (CMT4B1) is a motor and sensory neuropathy characterized pathologically by the presence of focally folded myelin sheaths. [from MIM:601382; 2022.12.21]
CMT4B1 is caused by homozygous mutation in the MTMR2 gene encoding the myotubularin-related protein-2. [from MIM:601382; 2022.12.21]
CMT4B1 is characterized pathologically by the presence of focally folded myelin sheaths. [from MIM:601382; 2022.12.21]
MTMR2 encodes a protein which is member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. [provided by RefSeq, Aug 2011]
The MTMR2 gene encodes a protein that belongs to the myotubularin family, which is characterized by the presence of a phosphatase domain (summary by Laporte et al., 1998, pmid:12925573). [from MIM:603557; 2022.12.21]
many to two (many human to 1 Drosophila); MTMR2 has one high-scoring Drosophila ortholog, mtm.
High-scoring ortholog of human MTMR2, MTM1, MTMR1; moderate scoring ortholog of human MTMR3, MTMR4, MTMR6, MTMR7 (1 Drosophila to many human).
