Identification of a novel PHOX2A gene mutation in a Chinese family with congenital fibrosis of extraocular muscles type 2 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate potential mutation of PHOX2A (or ARIX) gene in a Chinese family affected with congenital fibrosis of extraocular muscles tyep 2 (CFEOM2).</p><p><b>METHODS</b>Genomic DNA was obtained from affected and unaffected members of the family. With an ABI PRSIM Linkage Mapping Set-MD10 kit, selected markers flanking the PHOX2A locus were used for linkage analysis. Exons of PHOX2 gene were amplified and sequenced. A total of 100 normal subjects were recruited as controls.</p><p><b>RESULTS</b>Genetic linkage was found at 11q13 between D11S4151 and D11S1320 and the PHOX2A gene. DNA sequencing has identified a heterozygous mutation in the exon 2 of the gene (227T to G, N76K). The same mutation was not found in the unaffected and 100 normal controls.</p><p><b>CONCLUSION</b>A mutation of the PHOX2A gene 227T to G is responsible for the onset of congenital fibrosis of extraocular muscles type 2 in this Chinese family.</p>

Linkage analysis of a Chinese family with autosomal dominant congenital retinaochoroidal coloboma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To map the candidate gene by linkage analysis in a Chinese family with autosomal dominant congenital retinaochoroidal coloboma.</p><p><b>METHODS</b>A detailed clinical examination was performed for all patients in the family. The genomic DNA of all family members was extracted from peripheral blood leukocytes. Linkage analysis and genome-wide linkage screening was conducted using fluorescent detection of 398 microsatellite markers representing all autosomes at an average resolution of approximately 10 cM. Polymerase chain reaction was carried out to amplify all 398 microsatellite markers. The allele sizes were determined on ABI 3130-Avant genetic analyzer according to an internal size standard, and the results were analyzed using Genescan 3.1 and Genotyper 2.0 software.</p><p><b>RESULTS</b>Linkage analysis showed the markers D2S2382-D2S301-D2S2244-D2S163 co-segregated with the disease locus in all affected members. The maximum Lod score was 3.01(D2S2382).</p><p><b>CONCLUSION</b>The candidate region of the disease gene in the family was located in 2q34-2q35.</p>