科研之友
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摘要
Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with an autosomal dominant inheritance pattern. Individuals with Milroy disease are typically characterized by the congenital onset of lymphedema of the lower limbs as a result of the hypoplasia of the lymphatic vessels. A three-generation family in which Milroy disease segregates in an autosomal dominant manner was investigated. However, the affected family members did not suffer from the other clinical manifestations included hydrocele, ski jump toenails, and large caliber veins. Mutation analysis and functional studies were carried out in this pedigree. We screened VEGFR3 for mutations and identified a novel 3130 C>A transversion in exon 22, resulting in an L1044M missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele resulted in the development of lymphedema due to its segregation among each of the affected individuals. Functional studies demonstrated that compared with a previously reported mutation, c. 3059 A>T, the mutation in our pedigree appears to cause only a slight reduction in VEGFR3 downstream signaling. This may be the reason for the milder phonotype noted in this family. We identified a novel mutation that caused Milroy disease in a Chinese family. This is the first report describing the functional changes induced by the c. 3130 C>A mutation. This finding has expanded our knowledge of the VEGFR3 gene's function and has advanced our understanding of hereditary lymphedema.
