GM09276

GM09276 LCL from B-Lymphocyte

Description:

CARBOXYPEPTIDASE N DEFICIENCY
CARBOXYPEPTIDASE N, POLYPEPTIDE 1, 50-KD; CPN1

Affected:

Yes

Sex:

Male

Age:

73 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Other Disorders of Known Biochemistry

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Angioedema, about 40 attacks per year; urticaria on a few occasions during childhood; long-standing ragweed hay fever and asthma; proband and a sister have approximately 20% of normal carboxypeptidase N activity in serum; donor subject is a compound heterozygote: one allele has a frameshift mutation due to a single G insertion at nucleotide 385 (codon R58) in exon 1 of the CPN1 gene which predicted an abnormal and prematurely truncated protein of 164 amino acids [385fsInsG] and the second allele has a G>A transition at nucleotide 746 in exon 3 (746G>A) that results in a missense gly178-to-asp substitution [Gly178Asp (G178D)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

lysine carboxypeptidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.4.17.3; 20% activity.

Gene

CPN1

Chromosomal Location

10q24.2

Allelic Variant 1

603103.0001; CARBOXYPEPTIDASE N DEFICIENCY

Identified Mutation

1-BP INS, 385G; In the family originally reported by Mathews et al. (1980) in which carboxypeptidase N deficiency (212070) caused angioedema or chronic urticaria, as well as hay fever or asthma, Cao and Hegele (2003) found that the proband was an apparent compound heterozygote for 2 rare variants in the CPN1 gene: a frameshift mutation in exon 1 due to insertion of a single G at nucleotide 385, and a 746G-A transition in exon 3 that resulted in a gly178-to-asp substitution (G178D; 603103.0002).

Gene

CPN1

Chromosomal Location

10q24.2

Allelic Variant 2

603103.0002; CARBOXYPEPTIDASE N DEFICIENCY

Identified Mutation

GLY178ASP; In the family originally reported by Mathews et al. (1980) in which carboxypeptidase N deficiency (212070) caused angioedema or chronic urticaria, as well as hay fever or asthma, Cao and Hegele (2003) found that the proband was an apparent compound heterozygote for 2 rare variants in the CPN1 gene: a frameshift mutation in exon 1 due to insertion of a single G at nucleotide 385, and a 746G-A transition in exon 3 that resulted in a gly178-to-asp substitution (G178D; 603103.0002).

Phenotypic Data

Remarks

Publications

Cao H, Hegele RA, DNA polymorphism and mutations in CPN1, including the genomic basis of carboxypeptidase N deficiency. J Hum Genet48(1):20-2 2003

PubMed ID: 12560874

Mathews KP, Pan PM, Gardner NJ, Hugli TE, Familial carboxypeptidase N deficiency. Ann Intern Med93:443-5 1980

PubMed ID: 7437116

Mathews, Familial serum carboxypeptidase B deficiency with angioedema. J Allergy Clin Immunol63:186 (1979):443-5 1979

PubMed ID: 7437116

Mathews, Familial carboxypeptidase B deficiency with angioedema. Clin Res26:715A (1978):443-5 1978

PubMed ID: 7437116