title: A Truncating De Novo Point Mutation in a Young Infant with Severe Menkes Disease.
abstract: Menkes disease is a rare neurodegenerative disorder caused by mutations in ATP7A gene. Deficiency in copper-dependent enzymes results in the unique kinky hair appearance, neurodegeneration, developmental delay, seizures, failure to thrive and other connective tissue or organ abnormalities. Other than biochemical tests, DNA-based diagnosis is now playing an important role. More than two hundred mutations in ATP7A gene were identified. Early copper supplementation can help improve neurological symptoms, but not non-neurological problems. Further molecular studies are needed to identify additional mutation types and to understand the mechanism of pathogenesis. This may help in discovering the possible treatment measures to cure the disease. We present a case with the clinical features and biochemical findings, abnormal brain magnetic resonance imaging as well as the effects of treatment with copper-histidine. Direct sequencing of ATP7A gene revealed a de novo point mutation which resulted in an early stop codon with truncated protein.
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Che-Sheng
authors.initials: CS
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chyong-Hsin
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Chang-Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Ju-Li
authors.initials: JL
authors.lastname: Lin
authors.affiliation: Division of Biochemical Genetics, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chuang
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jen-Daw
authors.initials: JD
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Early Childhood Care and Education, Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
authors.forename: Nan-Chang
authors.initials: NC
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Division of Biochemical Genetics, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Early Childhood Care and Education, Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Division of Biochemical Genetics, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Early Childhood Care and Education, Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan. Electronic address: zsplin@ms2.mmh.org.tw.
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D006639:Histidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D009942:Organometallic Compounds / Q000627:therapeutic use; D017354:Point Mutation / Q000235:genetics*
chemical_list: D027682:Cation Transport Proteins; D009942:Organometallic Compounds; D006639:Histidine; C098468:copper histidine; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7A; Menkes disease; copper-histidine; de novo point mutation