Clinical and genetic analysis of a family with Kennedy disease

Abstract

Objective To identify the androgen receptor (AR) gene mutation in a pedigree with Kennedy disease. Methods Two Kennedy disease probands and six family members were collected. Routine detections including neurological examination, neurophysiological EMG and serum creatine kinase (CK) were preformed for two probands. Genomic DNA from eight peripheral venous blood samples was extracted. The repeat numbers of the trinucleotide CAG tandem-repeat in exon 1 of the AR gene were detected by polymerase chain reaction (PCR) amplification. PCR product was confirmed by 1.5% agarose gel electrophoresis, and abnormal samples were detected by DNA direct sequencing. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by capillary electrophoresis fragment analysis. Results EMG results of two probands showed that sensory and motor nerves were involved and serum CK was increased. The repeat numbers of the trinucleotide CAG tandem-repeat in exon 1 of the androgen receptor gene of two patients (Ⅲ1 and Ⅲ3) were 58 and 54, respectively. Four female carriers (Ⅱ1, Ⅱ3, Ⅲ5 and Ⅳ1) were found. The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅱ1 carrier were 22 and 58. The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅱ3 carrier were 22 and 54. The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅲ5 carrier were 24 and 54. The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅳ1 carrier were 20 and 61. The repeat number of the trinucleotide CAG tandem-repeat of two normal male samples was 24. Conclusion The repeat number of the trinucleotide CAG tandem-repeat of the family was unstable. Gene diagnosis can be used as a reliable basis for the diagnosis of Kennedy disease. AR gene mutation detection can help the family genetic counseling. It has important significance for the treatment and prevention of Kennedy disease. Key words: Kennedy disease; Androgen receptor gene; Gene diagnosis