Compound heterozygous POMGNT1 mutations leading to muscular dystrophy-dystroglycanopathy type A3: a case report

Abstract Background Dystroglycanopathies, which are caused by reduced glycosylation of alpha-dystroglycan, are a heterogeneous group of neurodegenerative disorders characterized by variable brain and skeletal muscle involvement. Muscle-eye-brain disease (or muscular dystrophy-dystroglycanopathy type 3 A) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and lissencephaly. Case presentation We report clinical and genetic characteristics of a 6-year-old boy affected by muscular dystrophy-dystroglycanopathy. He has severe a delay in psychomotor and speech development, muscle hypotony, congenital myopia, partial atrophy of the optic nerve disc, increased level of creatine kinase, primary-muscle lesion, polymicrogyria, ventriculomegaly, hypoplasia of the corpus callosum, cysts of the cerebellum. Exome sequencing revealed compound heterozygous mutations in POMGNT1 gene (transcript NM_001243766.1): c.1539 + 1G > A and c.385C > T. Conclusions The present case report shows diagnostic algorithm step by step and helps better understand the clinical and genetic features of congenital muscular dystrophy

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

Abstract Background Neuronal ceroid lipofuscinoses (NCLs) are the most common autosomal recessive neurodegenerative disorders in children. Clinical manifestations include progressive cognitive decline, motor impairment, ataxia, visual loss, seizures and early death. To date more than 440 NCL-causing mutations in 13 genes are known. Case presentation We report clinical and genetic characteristics of a 5-year-old girl affected by ceroid lipofuscinosis type 7 (NCL7). She had progressive motor and mental deterioration since the age of 2,5 years. Later she developed progressive vision loss, stereotypies, action myoclonus and epilepsy. By the age of 5 years she stopped walking. Based on symptoms, diagnosis of Rett syndrome was suggested, but no abnormalities were detected in MeCP2. We identified a novel homozygous mutation in MFSD8 gene (c.525 T > A, p.Cys175Ter). To our knowledge, this is the first report of MFSD8 gene mutation in a Russian patient with variant late-infantile NCL. Conclusions Our results enlarge mutational spectrum of ceroid lipofuscinosis type 7 and demonstrate tremendous diagnosis value of exome sequencing for pediatric NCLs. Also we confirmed that NCL should be suspected in patients with Rett-like phenotype at onset and negative MECP2 mutation