Alternative titles; symbols
ORPHA: 370959; DO: 0112378;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p34.1 | Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 | 613151 | Autosomal recessive | 3 | POMGNT1 | 606822 |
A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development (type B3; MDDGB3) is caused by homozygous or compound heterozygous mutation in the gene encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGNT1; 606822) on chromosome 1p34.
Mutation in the POMGNT1 gene can also cause a more severe congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A3; MDDGA3; 253280) and a less severe limb-girdle muscular dystrophy-dystroglycanopathy (type C3; MDDGC3; 613157).
MDDGB3 is an autosomal recessive congenital muscular dystrophy with impaired intellectual development and mild brain abnormalities (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2009).
For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Clement et al. (2008) reported a 16-year-old patient with POMGNT1-related congenital muscular dystrophy who had mental retardation, myopia, optic atrophy, and increased serum creatine kinase. Brain MRI showed ventricular dilatation, diffuse white matter changes, cerebellar cysts, and pontine hypoplasia.
Mercuri et al. (2009) identified 1 patient with POMGNT1-related congenital muscular dystrophy in a larger study of 81 patients with muscular dystrophy and evidence of a dystroglycanopathy. Although clinical details were limited, the patient had achieved walking, showed decreased alpha-dystroglycan on muscle biopsy, and had strabismus, myopia, and mental retardation. Brain MRI showed cerebellar cysts.
In a 16-year-old patient with congenital muscular dystrophy and mental retardation, Clement et al. (2008) identified compound heterozygosity for mutations in the POMGNT1 gene (606822.0015 and 606822.0016).
In an Italian patient with congenital muscular dystrophy and mental retardation, Mercuri et al. (2009) identified a homozygous mutation in the POMGNT1 gene (R605P; 606822.0014).
Clement, E., Mercuri, E., Godfrey, C., Smith, J., Robb, S., Kinali, M., Straub, V., Bushby, K., Manzur, A., Talim, B., Cowan, F., Quinlivan, R., and 10 others. Brain involvement in muscular dystrophies with defective dystroglycan glycosylation. Ann. Neurol. 64: 573-582, 2008. [PubMed: 19067344] [Full Text: https://doi.org/10.1002/ana.21482]
Mercuri, E., Messina, S., Bruno, C., Mora, M., Pegoraro, E., Comi, G. P., D'Amico, A., Aiello, C., Biancheri, R., Berardinelli, A., Boffi, P., Cassandrini, D. Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. Neurology 72: 1802-1809, 2009. Note: Erratum: Neurology 93: 371 only, 2019. [PubMed: 19299310] [Full Text: https://doi.org/10.1212/01.wnl.0000346518.68110.60]