Identification of a HPGD mutation in three families affected with primary hypertrophic osteoarthropathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutation of HPGD gene among three pedigrees affected with primary hypertrophic osteoarthropathy (PHO) by DNA sequencing and high-resolution melting (HRM) analysis.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples collected from the pedigrees. PCR and direct sequencing were carried out to identify potential mutations of the HPGD gene. Amplicons containing the mutation spot were generated by nested PCR. The products were then subjected to HRM analysis using the HR-1 instrument. Direct sequencing was carried out in family members and healthy individuals to confirm the result of HRM analysis.</p><p><b>RESULTS</b>A homozygous mutation c.310_311delCT was detected in 2 affected probands, while a heterozygous mutation c.310_311delCT was detected in the third proband. HRM analysis of the fragments encompassing HPGD exon 3 showed 3 curve patterns representing three different genotypes, i.e., the wild type, the c.310_311delCT homozygote, and the c.310_311delCT heterozygote. Result of DNA sequencing was consistent with that of the HRM analysis and phenotype of the subjects.</p><p><b>CONCLUSION</b>The c.310_311delCT mutation may be the most prevalent mutation among Chinese population. HRM analysis has provided an optimized method for genetic testing of HPGD mutation for its simplicity, rapid turnover and high sensitivity.</p>

Molecular diagnosis for a patient with Kennedy disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for potential mutations of androgen receptor (AR) gene in a patient clinically diagnosed as Kennedy disease.</p><p><b>METHODS</b>Polyglutamine expansion (PQE) induced by a duplication of CAG trinucleotide tandem-repeat in exon 1 of the AR gene was detected with PCR and T-clone sequencing.</p><p><b>RESULTS</b>Compared with the number of CAG repeat of 22 in the normal allele, the number of CAG repeats has increased to 45 in the mutant allele carried by the patient. This has fit with the diagnostic criteria for Kennedy disease.</p><p><b>CONCLUSION</b>A mutation of PQE has been detected in the patient with Kennedy disease. Detection of PQE in AR gene can be used as reliable method to identify the Kennedy disease.</p>