Novel USH2A compound heterozygous mutations cause RP/USH2 in a Chinese family

[摘要] Purpose: To identify the disease-causinggene in a four-generation Chinese family affected with retinitispigmentosa (RP). Methods: Linkage analysis was performedwith a panel of microsatellite markers flanking the candidate geneticloci of RP. These loci included 38 known RP genes. The complete codingregion and exon-intron boundaries of Usher syndrome 2A (USH2A)were sequenced with the proband DNA to screen the disease-causing genemutation. Restriction fragment length polymorphism (RFLP) analysis anddirect DNA sequence analysis were done to demonstrate co-segregation ofthe USH2A mutations with the family disease. One hundred normalcontrols were used without the mutations. Results: The disease-causing gene inthis Chinese family was linked to the USH2A locus on chromosome1q41. Direct DNA sequence analysis of USH2A identified twonovel mutations in the patients: one missense mutation p.G1734R in exon26 and a splice site mutation, IVS32+1G>A, which was found in thedonor site of intron 32 of USH2A. Neither the p.G1734R nor theIVS32+1G>A mutation was found in the unaffected family members orthe 100 normal controls. One patient with a homozygous mutationdisplayed only RP symptoms until now, while three patients withcompound heterozygous mutations in the family of study showed both RPand hearing impairment. Conclusions: This study identified twonovel mutations: p.G1734R and IVS32+1G>A of USH2A in afour-generation Chinese RP family. In this study, the heterozygousmutation and the homozygous mutation in USH2A may cause Ushersyndrome Type II or RP, respectively. These two mutations expand themutant spectrum of USH2A.

[学科分类] 生物化学/生物物理