This report describes muscular dystrophy, limb-girdle, autosomal recessive 29, a subtype of autosomal recessive limb-girdle muscular dystrophy. The human gene implicated is SNUPN, which encodes snurportin 1, a U snRNP-specific nuclear import adapter. There is one high-scoring fly ortholog, Dmel\Snup for which multiple genetic reagents, RNAi-targeting constructs have been generated.
Wild-type Hsap\SNUPN has been introduced into flies, but has not been used to model disease.
Muscle-specific RNAi knockdown of Dmel\Snup resulted in a progressive age-dependent reduction in mobility as assayed by climbing activity, and a decrease in longevity.
[updated Dec. 2024 by FlyBase; FBrf0222196]
Limb-girdle muscular dystrophy primarily affects the proximal muscles, resulting in difficulty walking. The age at onset varies, but most patients show onset in childhood, and the disorder is progressive. Involvement is first evident in either the pelvic or, less frequently, the shoulder girdle, often with asymmetry of wasting when the upper limbs are first involved; spread from the lower to the upper limbs or vice versa occurs within 20 years (Chung and Morton, 1959; pubmed:13810212). [from MIM:253600; 2016.03.11]
[MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 29; LGMDR29](https://omim.org/entry/620793)
[SNURPORTIN 1; SNUPN](https://omim.org/entry/607902)
Autosomal recessive limb-girdle muscular dystrophy-29 (LGMDR29) is a neuromuscular disorder characterized by onset of muscle weakness predominantly affecting the proximal lower limbs, although upper limb involvement also occurs. The disorder, which causes walking difficulties, is progressive and may result in loss of ambulation. Additional features include joint contractures, spinal abnormalities, and significant restrictive ventilatory dysfunction. Muscle biopsy shows dystrophic and myofibrillar changes, and serum creatine kinase is increased. Rare individuals have been reported to have central nervous system involvement, including cataracts, developmental delay, and brain imaging abnormalities (Nashabat et al., 2024, pubmed:38413582 and Iruzubieta et al., 2024, pubmed:38366623). [from MIM:620793; 2024.12.04]
Autosomal recessive limb-girdle muscular dystrophy-29 (LGMDR29) is caused by homozygous or compound heterozygous mutation in the SNUPN gene on chromosome 15q24. [from MIM:620793; 2024.12.04]
The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is dependent on the presence of a complex nuclear localization signal. The latter is composed of the 5'-2,2,7-terminal trimethylguanosine (m3G) cap structure of the U snRNA and the Sm core domain. The protein encoded by SNUPN interacts specifically with m3G-cap and functions as an snRNP-specific nuclear import receptor. [provided by RefSeq, Jul 2008]
The SNUPN gene encodes snurportin-1, a key adaptor protein important for nuclear import of small nuclear ribonucleoproteins (snRNPs), which are essential components of the spliceosome (summary by Nashabat et al., 2024, pubmed:38366623) [from MIM:607902; 2024.12.04]
MOne to one (1 human to 1 Drosophila); GRM1 has one high-scoring Drosophila ortholog, Snup.
High-scoring ortholog of human SNUPN (1 Drosophila to 1 human).
