Wilson's disease (WD), an autosomal recessive copper transport disorder, usually presents with symptoms involving the liver or central nervous system. The disease is caused by a large number of mutations in the ATP7B gene comprising 21 expressed exons. Some of the mutations appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This paper presents the results of screening of the ATP7B gene by means of the direct sequencing of all exons in the gene in 39 Han and one Hui ethnic Chinese patients. Nineteen novel mutations were revealed along with nine others that have been previously described; 57.5% of the mutations were located in exons 8, 13, and 12. In particular, the Arg778Leu mutation in exon 8 was found in 55% of these Chinese patients in at least one allele. Five patients were homozygotes and 17 patients were heterozygotes for Arg778Leu. The detection rate on direct sequencing of the polymerase chain reaction products of all exons of the ATP7B gene in 40 unrelated patients was 83.8% of alleles. Seventeen polymorphisms were also identified in patients and healthy controls. We first reported the presence of ATP7B mutations in Chinese Hui ethnic patients and summarize our results here along with the previously reported findings. A significant correlation between genotype and phenotype was not found in 37 homozygotes and 52 heterozygotes for Arg778Leu.

The myosin VIIA (MYO7A) gene encodes a protein classified as an unconventional myosin. Mutations within MYO7A can lead to both syndromic and non-syndromic hearing impairment in humans. Among different mutations reported in MYO7A, only five led to non-syndromic sensorineural deafness autosomal dominant type 11 (DFNA11). Here, we present the clinical, genetic and molecular characteristics of two large Chinese DFNA11 families with either high-or low-frequency hearing loss. Affected individuals of family DX-J033 have a sloping audiogram at young ages with high frequency are most affected. With increasing age, all test frequencies are affected. Affected members of family HB-S037 present with an ascending audiogram affecting low frequencies at young ages, and then all frequencies are involved with increasing age. Genome-wide linkage analysis mapped the disease loci within the DFNA11 interval in both families. DNA sequencing of MYO7A revealed two novel nucleotide variations, c.652G4A (p.D218N) and c.2011G4A (p.G671S), in the two families. It is for the first time that the mutations identified in MYO7A in the present study are being implicated in DFNA11 in a Chinese population. For the first time, we tested electrocochleography (ECochG) in a DFNA11 family with low-frequency hearing loss. We speculate that the low-frequency sensorineural hearing loss in this DFNA11 family was not associated with endolymphatic hydrops.

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