A novel splice site mutation in the dentin sialophosphoprotein gene in a Chinese family with dentinogenesis imperfecta type II.

[dentinogenesis imperfecta]

Twenty -four individuals were investigated that spanned six generations in a Chinese family affected with an apparently autosomal dominant form of dentinogenesis imperfecta type II (DGI -II , OMIM #125490 ). All affected individuals presented with typical , clinical and radiographic features of DGI -II , but without bilateral progressive high -frequency sensorineural hearing loss . To investigate the mutated molecule , a positional candidate approach was used to determine the mutated gene in this family . Genomic DNA was obtained from 24 affected individuals , 18 unaffected relatives of the family and 50 controls . Haplotype analysis was performed using leukocyte DNA for 6 short tandem repeat (STR ) markers present in chromosome 4 (D 4 S 1534 , GATA 6 2 A 11 , DSPP , DMP 1 , SPP 1 and D 4 S 1563 ). In the critical region between D 4 S 1534 and DMP 1 , the dentin sialophosphoprotein (DSPP ) gene (OMIM *125485 ) was considered as the strongest candidate gene . The first four exons and exon /intron boundaries of the gene were analyzed using DNA from 24 affected individuals and 18 unaffected relatives of the same family . DNA sequencing revealed a heterozygous deletion mutation in intron 2 (at positions -3 to -25 ), which resulted in a frameshift mutation , that changed the acceptor site sequence from CAG to AAG (IVS 2 -3 C-->A ) and may also have disrupted the branch point consensus sequence in intron 2 . The mutation was found in the 24 affected individuals , but not in the 18 unaffected relatives and 50 controls . The deletion was identified by allele-specific sequencing and denaturing high -performance liquid chromatography (DHPLC ) analysis . We conclude that the heterozygous deletion mutation contributed to the pathogenesis of DGI -II .

Diseases
Validation

Diseases presenting "apparently autosomal" symptom

dentinogenesis imperfecta

oligodontia

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