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Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiencyNorepinephrine (NE), a key neurotransmitter of the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) that catalyzes oxidation of dopamine (DA) to NE. NE deficiency is a congenital disorder of unknown etiology, in which affected patients suffer profound autonomic failure. Biochemical features of the syndrome include undetectable tissue and circulating levels of NE and epinephrine, elevated levels of DA, and undetectable levels of DBH. Here, we report identification of seven novel variants including four potentially pathogenic mutations in the human DBH gene (OMIM 223360) from analysis of two unrelated patients and their families. Both patients are compound heterozygotes for variants affecting expression of DBH protein. Each carries one copy of a T-->C transversion in the splice donor site of DBH intron 1, creating a premature stop codon. In patient 1, there is a missense mutation in DBH exon 2. Patient 2 carries missense mutations in exons 1 and 6 residing in cis. We propose that NE deficiency is an autosomal recessive disorder resulting from heterogeneous molecular lesions at DBH. Copyright 2002 Wiley-Liss, Inc.
Document ID
20040088450
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Kim, Chun-Hyung
(McLean Hospital, Harvard Medical School Belmont, Massachusetts, United States)
Zabetian, Cyrus P.
Cubells, Joseph F.
Cho, Sonhae
Biaggioni, Italo
Cohen, Bruce M.
Robertson, David
Kim, Kwang-Soo
Date Acquired
August 21, 2013
Publication Date
March 1, 2002
Publication Information
Publication: American journal of medical genetics
Volume: 108
Issue: 2
ISSN: 0148-7299
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL56693
CONTRACT_GRANT: MH 30929
CONTRACT_GRANT: DA-12422
CONTRACT_GRANT: MH48866
CONTRACT_GRANT: 5T32-DA-07238
CONTRACT_GRANT: DA-00167
Distribution Limits
Public
Copyright
Other
Keywords
Case Reports
Non-NASA Center
NASA Discipline Neuroscience

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