title: Two novel CAII mutations causing carbonic anhydrase II deficiency syndrome in two unrelated Chinese families.
abstract: The carbonic anhydrase II (CAII) deficiency syndrome is a rare autosomal recessive osteopetrosis with renal tubular acidosis (RTA) and cerebral calcifications (MIM259730). CAII deficiency syndrome is caused by mutations in the gene CAII, which encodes the enzyme carbonic anhydrase II. CAII mutations are rarely reported in the Asian population. Here, we described two unrelated CAII deficiency families of Chinese Han origin with clinical and genetic analysis. Altogether, 106 subjects, including 2 probands, 4 unaffected family members from two non-consanguineous Chinese families, and 100 healthy controls were recruited. All seven exons and the exon-intron boundaries of the CAII gene were amplified and directly sequenced. Reverse transcription PCR (RT-PCR) was used to study the effect of splice site mutation. All clinical and biochemical parameters of the probands were collected. Two novel mutations of CAII gene were identified by mutational analysis: A nonsense mutation in exon 4 (c.T381C p.Y127X) in both families; a splice mutation at the splice donor site of intron 3 (c.350+2T>C, IVS3+2T>C) in one family. The splice-site mutation causes exon 3 skipping in patient's mRNA resulting in an in-frame deletion and a novel premature stop codon. These mutations were predicted to result in a loss of function of CAII. This is the first report of CAII deficiency syndrome in Chinese population. Our findings extent the spectrum of CAII mutations observed in patients with CAII deficiency syndrome.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, The Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Pang
authors.forename: Xuan
authors.initials: X
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Jin
authors.initials: J
authors.lastname: Dong
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
mesh_terms: D000141:Acidosis, Renal Tubular / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000235:genetics*; D002256:Carbonic Anhydrases / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010022:Osteopetrosis / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases