BACKGROUNDDuchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becker muscular dystrophy (DMD/BMD), and to study genotype-phenotype correlation.

METHODSA retrospective review of 67 patients.

RESULTSTwenty-three (34.3%) patients had exon deletions; whereas 5 (7.5%) patients had exon duplications. Twenty-three (34.3%) patients had small mutations, including 17 point mutations and 6 small insertions or deletions. No correlation was found between the type of mutation and the muscle phenotype or mental retardation. Significantly fewer maternal carriers were found in patients with exon deletions, and a positive family history was more common in those with small mutations. DMD phenotype was significantly less common in patients with exon deletions/duplications at the 5' hotspot, whereas all 4 small mutations associated with mental retardation were located in the 3' end of the gene.

CONCLUSIONSThe percentage of DMD exon deletions in local Chinese patients was significantly lower than the commonly quoted 60%. This indicated an ethnic or regional difference in predisposition to DMD exon deletions.

Asian Continental Ancestry Group ; Dystrophin ; genetics ; Exons ; Genotype ; Heterozygote ; Humans ; Intellectual Disability ; genetics ; Muscular Dystrophy, Duchenne ; genetics ; Mutation ; Phenotype ; Polymerase Chain Reaction

Abnormalities, Multiple ; genetics ; Amino Acid Sequence ; Blepharophimosis ; genetics ; Blepharoptosis ; genetics ; Eyelids ; abnormalities ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Syndrome

Homeodomain Proteins ; genetics ; Humans ; Infant, Newborn ; Male ; Mutation ; Promoter Regions, Genetic ; Sleep Apnea, Central ; congenital ; genetics ; Syndrome ; Transcription Factors ; genetics

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics