PDF(Pubmed)
Abstract：
BACKGROUND: Usher Syndrome is the commonest cause of inherited blindness and deafness. The condition is clinically and genetically heterogeneous, with no current treatment. We report a case carrying novel biallelic variants in USH2A causing progressive early adolescent onset visual and hearing impairment consistent with Usher Syndrome Type IIA.
METHODS: Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual.
CONCLUSIONS: The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.
METHODS: Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual.
CONCLUSIONS: The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.
摘要：
背景：Usher综合征是遗传性失明和耳聋的最常见原因。这种情况在临床和遗传上是异质的，目前没有治疗。我们报告了一例在USH2A中携带新型双等位基因变体的病例，导致进行性青少年早期发作的视力和听力障碍，与IIA型Usher综合征一致。
方法：我们的患者在13岁时出现进行性视野丧失和听力丧失，与40多岁的白内障早期发病有关，需要摘除晶状体。现在52岁,最新的最佳矫正视力（BCVA）为Logmar右眼（RE）0.8和左眼（LE）0.2，双侧视野明显收缩。她的年龄为46岁。先证者的临床和分子遗传学评估与IIA型Usher综合征的诊断一致。基因检测确定了两个新的USH2A变体，导致提前终止密码子p.Leu30Ter和错义突变p.Cys3251Tyr.分离分析证实这些变体在受影响的病例中是双等位基因的。综合计算机分析证实，这些突变是该个体IIA型Usher综合征的可能原因。
结论：USH2A新突变的鉴定增加了导致Usher综合征的遗传变异谱，协助基因诊断,患者预后评估，并强调基因检测对于识别未确诊的进行性视力丧失患者的新突变的重要性。
方法：我们的患者在13岁时出现进行性视野丧失和听力丧失，与40多岁的白内障早期发病有关，需要摘除晶状体。现在52岁,最新的最佳矫正视力（BCVA）为Logmar右眼（RE）0.8和左眼（LE）0.2，双侧视野明显收缩。她的年龄为46岁。先证者的临床和分子遗传学评估与IIA型Usher综合征的诊断一致。基因检测确定了两个新的USH2A变体，导致提前终止密码子p.Leu30Ter和错义突变p.Cys3251Tyr.分离分析证实这些变体在受影响的病例中是双等位基因的。综合计算机分析证实，这些突变是该个体IIA型Usher综合征的可能原因。
结论：USH2A新突变的鉴定增加了导致Usher综合征的遗传变异谱，协助基因诊断,患者预后评估，并强调基因检测对于识别未确诊的进行性视力丧失患者的新突变的重要性。
