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.
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Acknowledgments
We appreciate our patients and their families for their participating in this study.
This study was supported by a grant from The Ministry of Science and Technology of the People’s Republic of China (National Science and Technology Major Projects for “Major New Drugs Innovation and Development” 2008ZX09312-016). National Natural Science Foundation of China (No. 81070687, 81470188 and 81170805), Beijing Natural Science Foundation (No. 7121012) and Scientific Research Foundation of Beijing Medical Development (No. 2007–3029). National Key Program of Clinical Science (WBYZ2011-873)
All listed authors have each made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; participated in drafting the manuscript or revising it critically for content; and have approved the final version of the submitted manuscript.
Dr. Qian-qian Pang and Prof. Wei-Bo Xia accept responsibility for the integrity of the data analysis.
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Pang, Q., Qi, X., Jiang, Y. et al. Two novel CAII mutations causing carbonic anhydrase II deficiency syndrome in two unrelated Chinese families. Metab Brain Dis 30, 989–997 (2015). https://doi.org/10.1007/s11011-015-9660-6
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DOI: https://doi.org/10.1007/s11011-015-9660-6