PMID- 10053004
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20211203
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 3
DP  - 1999 Mar
TI  - Human molybdopterin synthase gene: genomic structure and mutations in molybdenum 
      cofactor deficiency type B.
PG  - 706-11
AB  - Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the
      formation of a precursor and (2) the latter's subsequent conversion, by
      molybdopterin synthase, into the organic moiety of MoCo. These two steps are
      reflected by the complementation groups A and B and the two formally
      distinguished types of MoCo deficiency that have an identical phenotype. Both
      types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme
      activities and cause severe neurological damage. MOCS1 is defective in patients
      with group A deficiency and has been shown to encode two enzymes for early
      synthesis via a bicistronic transcript with two consecutive open reading frames
      (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via 
      a single transcript with two overlapping reading frames. This gene was mapped to 
      5q and comprises seven exons. The coding sequence and all splice site-junction
      sequences were screened for mutations, in MoCo-deficient patients in whom a
      previous search for MOCS1 mutations had been negative. In seven of the eight
      patients whom we investigated, we identified MOCS2 mutations that, by their
      nature, are most likely responsible for the deficiency. Three different
      frameshift mutations were observed, with one of them found on 7 of 14 identified 
      alleles. Furthermore, a start-codon mutation and a missense mutation of a highly 
      conserved amino acid residue were found. The locations of the mutations confirm
      the functional role of both ORFs. One of the patients with identified MOCS2
      mutations had been classified as type B, in complementation studies. These
      findings support the hypothetical mechanism, for both forms of MoCo deficiency,
      that formerly had been established by cell-culture experiments.
FAU - Reiss, J
AU  - Reiss J
AD  - Institut fur Humangenetik, Gosslerstrasse 12d, D-37073 Gottingen, Germany.
      jreiss@gwdg.de
FAU - Dorche, C
AU  - Dorche C
FAU - Stallmeyer, B
AU  - Stallmeyer B
FAU - Mendel, R R
AU  - Mendel RR
FAU - Cohen, N
AU  - Cohen N
FAU - Zabot, M T
AU  - Zabot MT
LA  - eng
GR  - GENBANK/AF091871/BA/FDA HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Coenzymes)
RN  - 0 (Metalloproteins)
RN  - 0 (Molybdenum Cofactors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oligonucleotides)
RN  - 0 (Pteridines)
RN  - ATN6EG42UQ (molybdenum cofactor)
RN  - EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors)
RN  - EC 2.8.1.- (Sulfurtransferases)
RN  - EC 2.8.1.- (molybdopterin synthase)
RN  - EC 4.1.- (Carbon-Carbon Lyases)
RN  - EC 4.1.- (MOCS1 protein, human)
SB  - IM
MH  - Carbon-Carbon Lyases
MH  - Cell Line
MH  - *Coenzymes
MH  - Exons
MH  - Fibroblasts
MH  - Genotype
MH  - Humans
MH  - Metabolic Diseases/etiology/genetics
MH  - Metalloproteins/*metabolism
MH  - Models, Genetic
MH  - Molybdenum Cofactors
MH  - Nuclear Proteins/genetics
MH  - Oligonucleotides
MH  - Oxidoreductases Acting on Sulfur Group Donors/metabolism
MH  - Pteridines/*metabolism
MH  - Sulfurtransferases/*genetics
PMC - PMC1377787
EDAT- 1999/03/03 03:04
MHDA- 2000/03/21 09:00
CRDT- 1999/03/03 03:04
PHST- 1999/03/03 03:04 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/03/03 03:04 [entrez]
AID - S0002-9297(07)61707-8 [pii]
AID - 10.1086/302296 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Mar;64(3):706-11. doi: 10.1086/302296.