Gene diagnosis and analysis of alkaptonuria in a Chinese pedigree

Abstract

Objective To study the clinical feature and genetic mutations of alkaptonuria(AKU). Methods One patient was diagnosed with AKU disease via gas chromatography mass spectrometry(GC/MS) in the investigated family.All exon of homogentisate 1, 2 dioxygenase(HGD) gene were amplified in the family by means of polymerase chain reaction(PCR) and followed by using direct DNA sequencing and Polyphen software was used to predict protein function. Results The infant only had red-brown urine, with no skin, joints, or viscera lesion, and GC/MS suggested AKU.Two heterozygous mutations of AKU were identified c. 34A>C(p.N12H) in exon 2 c. 240A>T(p.Q80H)in exon 4 and c. 910A>G(p.K304E)in exon 12 from the proband.The heterozygous change c. 34A>C(p.N12H) in exon 2 was found in the proband's mother and sister with normal phenotype.The proband's father had the heterozygous change c. 910A>G(p.K304E) in exon 12. Conclusions The proband is hetero-zygous compound AKU disease patient carrying on one allele with the c. 34A>C(p.N12H) mutation inherited from his mother and the other allele with the c. 910A>G(p.K304E) from his father.The parents and his sister are heterozygous carrier with normal phenotype.The p. N12H and p. K304E mutations are novel mutations not reported around world yet, which has the earliest onset age of AKU with the only symptom of dark urine. Key words: Alkaptonuria; Homogentisate 1, 2 dioxygenase; Gene mutation; Gene diagnosis