Novel cystathionine β-synthase gene mutations in a Filipino patient with classic homocystinuria.

Abstract

BACKGROUND:

Classic homocystinuria due to cystathionine β-synthase (CBS) deficiency is an autosomal recessive disorder of sulfur metabolism. Clinical manifestations include mental retardation, dislocation of the optic lens (ectopia lentis), skeletal abnormalities and a tendency to thromboembolic episodes. We present the first mutational analysis of CBS in a Filipino patient with classic homocystinuria.

METHODS:

Genomic DNA was extracted from peripheral blood collected from a diagnosed Filipino patient with classic homocystinuria. The entire coding region of CBS (17 exons) was amplified using polymerase chain reaction and bidirectionally sequenced using standard protocols.

RESULTS:

The patient was found to be compound heterozygous for two novel mutations, g.13995G>A [c.982G>A; p.D328K] and g.15860-15868dupGCAGGAGCT [c.1083-1091dupGCAGGAGCT; p. Q362-L364dupQEL]. Four known single-nucleotide polymorphisms (rs234706, rs1801181, rs706208 and rs706209) were also detected in the present patient's CBS. The patient was heterozygous for all the identified alleles.

CONCLUSIONS:

This is the first mutational analysis of CBS done in a Filipino patient with classic homocystinuria who presented with a novel duplication mutation and a novel missense mutation. Homocystinuria due to CBS deficiency is a heterogeneous disorder at the molecular level.

• Authors: Catherine Lynn T Silao, Terence Diane F Fabella, Kahlil Izza D Rama, Sylvia C Estrada
• Journal: Pediatrics international : official journal of the Japan Pediatric Society (Pediatr Int) Vol. 57 Issue 5 Pg. 884-7 (Oct 2015) ISSN: 1442-200X [Electronic] Australia
• PMID: 25939784 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Japan Pediatric Society.

Chemical References

• DNA
• Cystathionine beta-Synthase

Topics

• Adolescent
• Alleles
• Cystathionine beta-Synthase (genetics, metabolism)
• DNA (genetics)
• DNA Mutational Analysis
• Female
• Genotype
• Homocystinuria (enzymology, genetics)
• Humans
• Mutation
• Philippines