GNE myopathy associated with congenital thrombocytopenia: A report of two siblings

Abstract GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congeni...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2014-12, Vol.24 (12), p.1068-1072
Main Authors: Izumi, Rumiko, Niihori, Tetsuya, Suzuki, Naoki, Sasahara, Yoji, Rikiishi, Takeshi, Nishiyama, Ayumi, Nishiyama, Shuhei, Endo, Kaoru, Kato, Masaaki, Warita, Hitoshi, Konno, Hidehiko, Takahashi, Toshiaki, Tateyama, Maki, Nagashima, Takeshi, Funayama, Ryo, Nakayama, Keiko, Kure, Shigeo, Matsubara, Yoichi, Aoki, Yoko, Aoki, Masashi
Format: Article
Language:English
Subjects:
Adult
Blood Platelets - pathology
Blood Platelets - physiology
Distal myopathy with rimmed vacuoles
Exome sequencing
Female
GNE
Humans
Male
Multienzyme Complexes - genetics
Muscle, Skeletal - pathology
Muscle, Skeletal - physiopathology
Muscular Diseases - genetics
Muscular Diseases - pathology
Muscular Diseases - physiopathology
Mutation
Neurology
Sialic acid
Siblings
Thrombocytopenia
Thrombocytopenia - genetics
Thrombocytopenia - pathology
Thrombocytopenia - physiopathology
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
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Summary:Abstract GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2014.07.008