Novel cystathionine β-synthase gene mutations in a Filipino patient with classic homocystinuria.
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.
Institute of Human Genetics, National Institutes of Health Philippines.|Department of Pediatrics, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
Catherine Lynn T
CL
Silao
Institute of Human Genetics, National Institutes of Health Philippines.
Terence Diane F
TD
Fabella
Institute of Human Genetics, National Institutes of Health Philippines.
Kahlil Izza D
KI
Rama
Institute of Human Genetics, National Institutes of Health Philippines.|Department of Pediatrics, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
Sylvia C
SC
Estrada
D000293:Adolescent; D000483:Alleles; D003541:Cystathionine beta-Synthase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006712:Homocystinuria / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010679:Philippines
D004247:DNA; D003541:Cystathionine beta-Synthase
Filipino; cystathionine beta-synthase; homocystinuria; mutation