Nobuhiko Okamoto1, Fuyuki Miya2,3,4, Yukihiro Kitai5, Tatsuhiko Tsunoda2,3,4, Mitsuhiro Kato6, Shinji Saitoh7, Yonehiro Kanemura8,9, Kenjiro Kosaki10. 1. Department of Medical Genetics, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan. okamoto@osaka.email.ne.jp. 2. Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. 3. Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 4. Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. 5. Department of Pediatric Neurology, Bobath Memorial Hospital, Osaka, Japan. 6. Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan. 7. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 8. Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan. 9. Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan. 10. Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: Mutations of theADCY5 have been identified in patients with familial dyskinesia, early-onsetautosomal dominant chorea and dystonia, and benign hereditary chorea. Most ofthe ADCY5 mutations are de novo or transmitted in an autosomal dominantfashion. Only two pedigrees are known to show autosomal recessive inheritance. OBJECTIVES: We report twosiblings with severe ID, dystonic movement, and growth failure with unknownetiology. METHODS: We planned a proband-parentapproach using whole exome sequencing. RESULTS: Homozygous mutationin exon 21 of the ADCY5 (p.R1238W) was identified in the siblings. Althoughtheir parents were heterozygous for the mutation, they were free from clinicalmanifestations. CONCLUSIONS: Our results furtherexpand the phenotype/genotype correlations of the ADCY5-related disorders.Mutations of ADCY5 should be considered in pediatric patients with ID andinvoluntary movement.
BACKGROUND: Mutations of theADCY5 have been identified in patients with familial dyskinesia, early-onsetautosomal dominant chorea and dystonia, and benign hereditary chorea. Most ofthe ADCY5 mutations are de novo or transmitted in an autosomal dominantfashion. Only two pedigrees are known to show autosomal recessive inheritance. OBJECTIVES: We report twosiblings with severe ID, dystonic movement, and growth failure with unknownetiology. METHODS: We planned a proband-parentapproach using whole exome sequencing. RESULTS: Homozygous mutationin exon 21 of the ADCY5 (p.R1238W) was identified in the siblings. Althoughtheir parents were heterozygous for the mutation, they were free from clinicalmanifestations. CONCLUSIONS: Our results furtherexpand the phenotype/genotype correlations of the ADCY5-related disorders.Mutations of ADCY5 should be considered in pediatric patients with ID andinvoluntary movement.
Entities:
Keywords:
ADCY5; Dyskinesia; Intellectual disability; Movement disorder
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