Genetic analysis of a Chinese pedigree with split hand and foot malformation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical manefestation and genetic basis of split hand and foot malformation (SHFM) in a Chinese pedigree.</p><p><b>METHODS</b>The affected people in the family were checked by X-rays. Eighteen patients provided their peripheral blood, and the genomic DNA of the samples was extracted. The linkage and haplotype analysis were carried out using the microsatellite markers, and the limb malformation related gene Dactylin (DAC) including the coding region, exon-intron boundaries and part of promoter region was sequenced.</p><p><b>RESULTS</b>Most members of the family with the disease phenotype showed absence or hypoplasia of the index finger, and absence or 3-4 syndactyly of the middle finger. The degree of abnormality in feet was severer than that in hands. All phenotypes of the patients display the basic characters of SHFM. Since the maximum two point LOD score of the D10S192 was 3.50 (theta=0.00), the SHFM in this pedigree can be categorized to the SHFM3. The haplotype analysis of recombination events revealed the candidate locus to a 21cM region between D10S185 and D10S1693. No mutation was found by the sequencing result of DAC gene.</p><p><b>CONCLUSION</b>Through the analysis of phenotype of the patients, the typical SHFM disease can be confirmed. The linkage and haplotype analysis demonstrated that the 21cM region in 10q23-q26 locus was the major cause to the disease in this pedigree. The mutation of DAC gene can be excluded from cause of SHFM3 phenotype.</p>

Mutation analysis of 12S rRNA and tRNA-Ser(UCN) genes in a large Chinese family with maternally inherited nonsyndromic hearing loss by intermarriage / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the possible mutation at possible sites in different mitochondrial genes that leads to hearing loss in a large Chinese pedigree.</p><p><b>METHODS</b>Blood samples from a Hunan pedigree were obtained with informed consent. Genomic DNA was extracted from peripheral blood leukocytes using kit. The target fragments were amplified and detected by polymerase chain reaction (PCR) and directly sequencing respectively.</p><p><b>RESULTS</b>The result of direct sequencing revealed the A1555G mutation in 12S rRNA gene was inherited in this pedigree and no one has A7445G mutation or other mutations in its neighborhood region.</p><p><b>CONCLUSION</b>Sequence analysis confirmed that the pedigree carries the A1555G mutation. With some members ever exposure of aminoglycoside antibiotics, mutation of A1555G may play a pivotal role in the pathogenesis of hearing loss in the large pedigree.</p>