DEMONSTRATION OF THE SPF-ASH MUTATION IN SPANISH PATIENTS WITH ORNITHINE TRANSCARBAMYLASE DEFICIENCY OF MODERATE SEVERITY

Citation
Ma. Garciaperez et al., DEMONSTRATION OF THE SPF-ASH MUTATION IN SPANISH PATIENTS WITH ORNITHINE TRANSCARBAMYLASE DEFICIENCY OF MODERATE SEVERITY, Human genetics, 95(2), 1995, pp. 183-186
Citations number
23
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
03406717
Volume
95
Issue
2
Year of publication
1995
Pages
183 - 186
Database
ISI
SICI code
0340-6717(1995)95:2<183:DOTSMI>2.0.ZU;2-#
Abstract
We have found in patients with ornithine transcarbamylase (OTC) defici ency from two Spanish families (A and B), replacement by A of G at the 3'-end of exon 4 of the OTC gene. The same mutation is found in the s pf-ash mouse, a rodent model of mild OTC deficiency, causing a neutral R129H mutation and inefficient splicing at the 5' donor site of the e xon 4-intron 4 junction, with resultant 4%-7% residual OTC activity. T he mutation, detected in our patients using polymerase chain reaction (PCR) amplification of the ten OTC exons, single strand conformation p olymorphism (SSCP) analysis and direct sequencing of PCR-amplified exo n 4, results in the loss of a unique MspI restriction site which can b e used for rapid diagnosis. The mutation was transmitted by the mother in family A and arose de novo in the patient in family B. Residual OT C activity, determined in a male and a female patient, was 1.3% and 3. 5% of normal, respectively. Despite this low activity, the surviving p atients have developed normally.