Analysis of the IDS Gene in 38 Patients with Hunter Syndrome: The c.879G>A (p.Gln293Gln) Synonymous Variation in a Female Create Exonic Splicing

作者：Zhang, Huiwen^*; Li, Jing; Zhang, Xinshun; Wang, Yu; Qiu, Wenjuan; Ye, Jun; Han, Lianshu; Gao, Xiaolan; Gu, Xuefan

来源：PLos One, 2011, 6(8): e22951.

DOI：10.1371/journal.pone.0022951

• MUCOPOLYSACCHARIDOSIS TYPE-II
• IDURONATE-2-SULFATASE GENE
• MPS-II
• MUTATION ANALYSIS
• STRUCTURAL-ANALYSIS
• JAPANESE PATIENTS
• MOLECULAR-BASIS
• DISEASE
• DIAGNOSIS
• MILD

Background: Hunter syndrome (mucopolysaccharidosis type II, MPS II) is a rare disease inherited in an X-linked autosomal recessive pattern. It is the prevailing form of the mucopolysaccharidoses in China. Here we investigated mutations of IDS (iduronate 2-sulfatase) gene in 38 unrelated Chinese patients, one of which is a female. @@@ Methods: Peripheral leucocytes were collected from the patients and the IDS gene was amplified to looking for the variations. For a female patient, the X chromosome status was analyzed by androgen receptor X-inactivation assay and the mutation impact on RNA level was further performed by reverse transcription polymerase chain reaction. @@@ Results: We discovered that point mutations constituted the major form while mutations in codon p.R468 defined the largest number of patients in our cohort. Consistent with data from other ethnic groups, exons 9 and 3 had comparatively more mutations, while exon 2 had quite a few mutations unique to Chinese patients. Of the 30 different mutations identified, only 9 were novel: one was a premature termination mutation, i.e., c.196C > T (p.Gln66X); three were missense mutations, i.e., c.200T > C (p.Leu67Pro), c.215T > C (p.Leu72Pro), c.389C > T (p.Thr130Ile); one was a small deletion, i.e., c.1104_1122del19 (p.Ser369ArgfsX16); and one was a deletion that spanned both exons 8 and 9 deletion leading to gross structural changes in the IDS gene. In addition, a synonymous mutation c.879G > A (p.Gln293Gln) was identified in a female Hunter disease patient, which resulted in loss of the original splicing site, activated a cryptic splicing site upstream, leading to a 28 bp deletion and a premature termination at p. Tyr285GlufsX47. Together with concurrent skewed X-inactivation this was believed to facilitate the development of Hunter disease in this girl. @@@ Conclusions: In conclusion, the molecular analysis of IDS gene in Chinese patients confirmed the Hunter disease diagnosis and expanded the mutation and clinical spectrum of this devastating disorder.

• 出版日期2011-8-4
• 单位上海交通大学