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

• Published in: Pediatrics international 2015-10, Vol.57 (5), p.884-887
• Main Authors: Silao, Catherine Lynn T., Fabella, Terence Diane F., Rama, Kahlil Izza D., Estrada, Sylvia C.
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; cystathionine beta-synthase; Cystathionine beta-Synthase - genetics; Cystathionine beta-Synthase - metabolism; DNA - genetics; DNA Mutational Analysis; Female; Filipino; Genotype; homocystinuria; Homocystinuria - enzymology; Homocystinuria - genetics; Humans; Mutation; Philippines
• ISSN: 1328-8067; 1442-200X
• DOI: 10.1111/ped.12666

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.