Skelet Muscle. 2015 Aug 28;5:29. doi: 10.1186/s13395-015-0056-4. eCollection 2015.

Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype.


BACKGROUND: Transport protein particle (TRAPP) is a multiprotein complex involved in endoplasmic reticulum-to-Golgi trafficking. Zebrafish with a mutation in the TRAPPC11 orthologue showed hepatomegaly with steatosis and defects in visual system development. In humans, TRAPPC11 mutations have been reported in only three families showing limb-girdle muscular dystrophy (LGMD) or myopathy with movement disorders and intellectual disability.
METHODS: We screened muscular dystrophy genes using next-generation sequencing and performed associated molecular and biochemical analyses in a patient with fatty liver and cataract in addition to infantile-onset muscle weakness.
RESULTS: We identified the first Asian patient with TRAPPC11 mutations. Muscle pathology demonstrated typical dystrophic changes and liver biopsy revealed steatosis. The patient carried compound heterozygous mutations of a previously reported missense and a novel splice-site mutation. The splice-site change produced two aberrantly-spliced transcripts that were both predicted to result in translational frameshift and truncated proteins. Full-length TRAPPC11 protein was undetectable on immunoblotting.
CONCLUSION: This report widens the phenotype of TRAPPC11-opathy as the patient showed the following: (1) congenital muscular dystrophy phenotype rather than LGMD; (2) steatosis and infantile-onset cataract, both not observed in previously reported patients; but (3) no ataxia or abnormal movement, clearly indicating that TRAPPC11 plays a physiological role in multiple tissues in human.


TRAPPC11遺伝子の新規変異によって、骨格筋障害・白内障・脂肪肝という表現型を来した例を世界で初めて見いだした。 筋ジストロフィー遺伝子パネルを作成し、次世代シークエンサーIonPGMを用いて網羅的に疾患原因既知遺伝子の解析を行うことによって、TRAPPC11 遺伝子に、これまでに知られていなかった変異をもつ例を見いだした。TRAPPC11遺伝子変異の報告はこれまでに1 報あるのみで、過去の論文では、シリア人1家系で見いだされた変異と北米フッター派2家系見いだされた変異が報告されていたが、今回の発見は、世界で第4 家系目でありアジアで初めての報告である。さらに、この家系では、これまで報告されている3家系と異なり、骨格筋だけでなく、白内障や肝臓の障害も認められた。遺伝子変異と臨床症状との関係を確立していく上で重要な発見であり、今後の病 気のメカニズムの解明や治療法の開発に寄与するものと考えられた。

PMID:  26322222