Abstract
Ornithine transcarbamylase (ornithine carbamoyl-transferase, EC 2.1.3.3) deficiency is an X-linked inborn error of metabolism with considerable phenotypic variability in affected males. Using a combination of the polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE), we defined a mutation in a family in whom affected males have significant residual enzyme activity. A C → T change in the first nucleotide of codon 277 resulted in the substitution of a tryptophan for an arginine at amino acid 245 of the mature protein. This change appears to represent a deleterious mutation rather than a polymorphism on the basis of several factors: the change occurs at a highly conserved arginine residue, significant size and change differences exist between arginine and tryptophan, and this change was not seen on DGGE screening of 26 unrelated individuals representing 43 chromosomes. Diagnosis of an at-risk male newborn in this family was performed using direct mutational analysis. In families with partial enzyme deficiencies in whom biochemical data may be difficult to evaluate, direct detection of mutations at the OTC locus permits definitive diagnosis. This represents the first description of a mutation in late onset OTC deficiency and demonstrates direct mutational analysis by DGGE for prospective diagnosis in a genetic disorder.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 167-172 |
| Number of pages | 6 |
| Journal | Genomics |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1990 |
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ASJC Scopus subject areas
- Genetics
Cite this
Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency. / Finkelstein, Janice E.; Francomano, Clair Ann; Brusilow, Saul W.; Traystman, Monica D.
In: Genomics, Vol. 7, No. 2, 1990, p. 167-172.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency
AU - Finkelstein, Janice E.
AU - Francomano, Clair Ann
AU - Brusilow, Saul W.
AU - Traystman, Monica D.
PY - 1990
Y1 - 1990
N2 - Ornithine transcarbamylase (ornithine carbamoyl-transferase, EC 2.1.3.3) deficiency is an X-linked inborn error of metabolism with considerable phenotypic variability in affected males. Using a combination of the polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE), we defined a mutation in a family in whom affected males have significant residual enzyme activity. A C → T change in the first nucleotide of codon 277 resulted in the substitution of a tryptophan for an arginine at amino acid 245 of the mature protein. This change appears to represent a deleterious mutation rather than a polymorphism on the basis of several factors: the change occurs at a highly conserved arginine residue, significant size and change differences exist between arginine and tryptophan, and this change was not seen on DGGE screening of 26 unrelated individuals representing 43 chromosomes. Diagnosis of an at-risk male newborn in this family was performed using direct mutational analysis. In families with partial enzyme deficiencies in whom biochemical data may be difficult to evaluate, direct detection of mutations at the OTC locus permits definitive diagnosis. This represents the first description of a mutation in late onset OTC deficiency and demonstrates direct mutational analysis by DGGE for prospective diagnosis in a genetic disorder.
AB - Ornithine transcarbamylase (ornithine carbamoyl-transferase, EC 2.1.3.3) deficiency is an X-linked inborn error of metabolism with considerable phenotypic variability in affected males. Using a combination of the polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE), we defined a mutation in a family in whom affected males have significant residual enzyme activity. A C → T change in the first nucleotide of codon 277 resulted in the substitution of a tryptophan for an arginine at amino acid 245 of the mature protein. This change appears to represent a deleterious mutation rather than a polymorphism on the basis of several factors: the change occurs at a highly conserved arginine residue, significant size and change differences exist between arginine and tryptophan, and this change was not seen on DGGE screening of 26 unrelated individuals representing 43 chromosomes. Diagnosis of an at-risk male newborn in this family was performed using direct mutational analysis. In families with partial enzyme deficiencies in whom biochemical data may be difficult to evaluate, direct detection of mutations at the OTC locus permits definitive diagnosis. This represents the first description of a mutation in late onset OTC deficiency and demonstrates direct mutational analysis by DGGE for prospective diagnosis in a genetic disorder.
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UR - http://www.scopus.com/inward/citedby.url?scp=0025281536&partnerID=8YFLogxK
U2 - 10.1016/0888-7543(90)90537-5
DO - 10.1016/0888-7543(90)90537-5
M3 - Article
C2 - 2347583
AN - SCOPUS:0025281536
VL - 7
SP - 167
EP - 172
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 2
ER -