Database: PubMedEntry: 16134170
Original site: 16134170
Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y.
Mutations in the holocarboxylase synthetase gene HLCS.
Hum Mutat. 2005 Oct;26(4):285-90. doi: 10.1002/humu.20204.
Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder.
HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and
histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS
gene have been reported. Mutations occur throughout the entire coding region
except exons 6 and 10. The types of mutations are one single amino acid deletion,
five single nucleotide insertions/deletions, 22 missense mutations, and two
nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A
(also designated IVS10+5G>A), which causes a splice error. Several lines of
evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients.
Prevalence of this mutation is about 10 times higher in the Faroe Islands than in
the rest of the world. The mutations p.L237P and c.780delG are predominant only
in Japanese patients. These are probably founder mutations in this population.
Mutations p.R508W and p.V550M are identified in several ethic groups and
accompanied with various haplotypes, suggesting that these are recurrent
mutations. There is a good relationship between clinical biotin responsiveness
and the residual activity of HLCS. A combination of a null mutation and a point
mutation that shows less than a few percent of the normal activity results in
neonatal onset. Patients who have mutant HLCS with higher residual activity
develop symptom after the neonatal period and show a good clinical response to
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