PMID- 10190325
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20061115
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 104
IP  - 2
DP  - 1999 Feb
TI  - Identification and characterization of mutations in patients with holocarboxylase
      synthetase deficiency.
PG  - 143-8
AB  - Holocarboxylase synthetase deficiency (HCS) is an autosomal recessive disorder
      characterized by metabolic ketoacidosis, abnormal urine organic metabolites, and 
      dermatitis. These symptoms are improved by pharmacological doses of biotin. In
      this study, we have analyzed seven patients with HCS deficiency found in European
      and Middle Eastern countries by using reverse transcription/polymerase chain
      reaction/single-stranded conformation polymorphism and a sequencing analysis.
      Although we had previously reported that two mutations were frequent in Japanese 
      patients, no frequent mutations were found in the patients analyzed in this
      study. Seven novel mutations were identified in the cDNA of the patients; these
      included three missense mutations, two single-base deletions that resulted in a
      termination codon, a three-base in-frame deletion, and a 68-bp deletion. A new
      polymorphism C1121T was also identified in four alleles. A transient expression
      study demonstrated that the HCS activities of three missense mutations and one
      amino acid deletion were 1%-14% that of wild-type cDNA; in contrast, the
      activities of the two single-base deletions followed by a termination codon and
      Asp571Asn were nearly undetectable. These data suggest that a variety of
      mutations is responsible for decreasing HCS activity and that the aspartate
      residue at amino acid position 571 may be crucial for the catalytic activity of
      HCS.
FAU - Aoki, Y
AU  - Aoki Y
AD  - Department of Medical Genetics, Tohoku University School of Medicine, Sendai,
      Japan.
FAU - Li, X
AU  - Li X
FAU - Sakamoto, O
AU  - Sakamoto O
FAU - Hiratsuka, M
AU  - Hiratsuka M
FAU - Akaishi, H
AU  - Akaishi H
FAU - Xu, L
AU  - Xu L
FAU - Briones, P
AU  - Briones P
FAU - Suormala, T
AU  - Suormala T
FAU - Baumgartner, E R
AU  - Baumgartner ER
FAU - Suzuki, Y
AU  - Suzuki Y
FAU - Narisawa, K
AU  - Narisawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - EC 6.3.- (Carbon-Nitrogen Ligases)
RN  - EC 6.3.4.- (holocarboxylase synthetases)
SB  - IM
MH  - Carbon-Nitrogen Ligases/deficiency/*genetics
MH  - Gene Expression Regulation
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - *Mutation
EDAT- 1999/04/06 00:00
MHDA- 1999/04/06 00:01
CRDT- 1999/04/06 00:00
PHST- 1999/04/06 00:00 [pubmed]
PHST- 1999/04/06 00:01 [medline]
PHST- 1999/04/06 00:00 [entrez]
PST - ppublish
SO  - Hum Genet. 1999 Feb;104(2):143-8.