GM11576

GM11576 Amniotic fluid-derived cell line from Amniotic fluid

Description:

HOLOCARBOXYLASE SYNTHETASE DEFICIENCY
HOLOCARBOXYLASE SYNTHETASE; HLCS

Affected:

Yes

Sex:

Female

Age:

16 FW (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Biopsy Source

Amniotic fluid

Cell Type

Amniotic fluid-derived cell line

Transformant

Untransformed

Sample Source

Amniotic fluid-derived cell line from Amniotic fluid

Race

White

Ethnicity

GERMAN

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Amniocytes have <1% of control holocarboxylase synthetase activity; pyruvate carboxylase, propionyl CoA carboxylase, & 3-methylcrotonyl CoA carboxylase enzyme activities were also very low; 2 affected sibs; slow growing culture; donor subject is a compound heterozygote: one allele has a IVS10+5G>A mutation in the HCLS gene and a second allele has a proline for leucine substitution at codon 514 [Leu514Pro (L514P)]

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

biotin--[propionyl-CoA-carboxylase (ATP-hydrolyzing)] ligase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 6.3.4.10; <1% activity.

Gene

HLCS

Chromosomal Location

21q22.1

Allelic Variant 1

253270.0007; HOLOCARBOXYLASE SYNTHETASE DEFICIENCY

Identified Mutation

IVS10+5G>A; In a large survey of HLCS mutations in patients with biotin-responsive MCD (253270), Yang et al. (Hum Genet 109:526-534,2001) identified an IVS10+5G-A mutation in 6 patients: 2 patients from the Faroe Islands and a Spanish and a Danish patient were homozygous for the mutation; and a French and a German patient were heterozygous. The haplotype of the HLCS gene in all 6 patients was identical, suggesting a founder mutation.

Gene

HLCS

Chromosomal Location

21q22.1

Allelic Variant 2

L514P; HOLOCARBOXYLASE SYNTHETASE DEFICIENCY

Identified Mutation

LEU514PRO