| #606070 | ||||||||||||
| MYOPATHY, DISTAL, 2; MPD2 | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| VOCAL CORD AND PHARYNGEAL DYSFUNCTION WITH DISTAL MYOPATHY; VCPDM | ||||||||||||
| Phenotype Gene Relationships | ||||||||||||
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| Clinical Synopsis | ||||||||||||
| TEXT | ||||||||||||
| A number sign (#) is used with this entry because this form of distal myopathy is caused by mutation in the matrin-3 gene on chromosome 5q31 (MATR3; 164015). | ||||||||||||
| Clinical Features | ||||||||||||
| Feit et al. (1998) described a large American family segregating an autosomal dominant distal myopathy, with multiple affected individuals in whom vocal cord and pharyngeal weakness may accompany the distal myopathy, without involvement of the ocular muscles. From a histopathologic standpoint, the lesion observed in these individuals was a noninflammatory myopathy with rimmed vacuoles probably fitting into the spectrum of the inclusion-bodied myopathies. Overall, the myopathy was mild or moderate. They stated that this 'form of distal myopathy has not been previously recognized and is distinct from other myopathies with pharyngeal or vocal weakness.' They referred to the clinical disorder as VCPDM (vocal cord and pharyngeal dysfunction with distal myopathy). Senderek et al. (2009) expanded the family described by Feit et al. (1998) with 2 additional sibs from an additional branch of the family. They also described a multigenerational Bulgarian family with a typical VCPDM phenotype. | ||||||||||||
| Diagnosis | ||||||||||||
| Differential Diagnosis Feit et al. (1998) commented on the possible confusion of the MPD2 phenotype with the axonal (neuronal) form of Charcot-Marie-tooth disease, CMT2 (see CMT2A1; 118210), if EMG results show a neurogenic disorder with normal nerve conduction velocities. Muscle biopsy would be required to distinguish between the 2 disorders. They also noted that the diagnosis of MPD2 does not require voice and pharyngeal changes, since some affected individuals in the kindred they studied did not show these changes at the time of examination. Two myopathies had already been mapped to 5q, the autosomal recessive limb-girdle muscular dystrophy (LGMD) 2F (601287) and the autosomal dominant LGMD1A (159000). LGMD2F was excluded because it was found to lie outside the linkage interval of MPD2. LGMD1A was encompassed by the linkage interval of MPD2, but the phenotypes of the 2 disorders were clinically quite different. Proximal weakness in LGMD1A is always much more severe than the distal weakness, whereas the opposite is observed in MPD2. Feit et al. (1998) noted that Young and Harper (1980) had described a similar autosomal dominant disorder with distal atrophy and vocal cord paralysis (158580) that mapped to chromosome 2. | ||||||||||||
| Mapping | ||||||||||||
| By use of combined genome screening and DNA pooling adapted to fluorescent markers, Feit et al. (1998) mapped the gene for the disorder, which they designated MPD2, to 5q, within a 12-cM interval between markers D5S458 and D5S1972 in this large pedigree (maximum lod score = 12.94 at a recombination fraction of 0.0 for D5S393). In the family originally described by Feit et al. (1998), Senderek et al. (2009) reduced the candidate interval to a 5.37-Mb region on chromosome 5q31, between short tandem repeat (STR) markers sara2AC and AC008667C. | ||||||||||||
| Nomenclature | ||||||||||||
| Feit et al. (1998) adopted the gene symbol MPD2 following the precedent of Laing et al. (1995), who had designated a form of distal myopathy that maps to 14q as MPD1 (160500). | ||||||||||||
| Molecular Genetics | ||||||||||||
| In the family described by Feit et al. (1998) and in an unrelated Bulgarian family with vocal cord and pharyngeal weakness with distal myopathy, Senderek et al. (2009) identified the same heterozygous missense mutation in the MATR3 gene (S85C; 164015.0001), which encodes a component of the nuclear matrix. | ||||||||||||
| REFERENCES | ||||||||||||
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