Department of Ophthalmology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, No.10 eastern section of the third fengcheng Road, Xi'an, 710018, China.
BMC Ophthalmol. 2023 Apr 11;23(1):151. doi: 10.1186/s12886-023-02905-5.
Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that may affect multiple systems of the body. Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by autosomal recessively mutations in bestrophin 1 (BEST1) gene. So far, we have not retrieved any case report of the same patient with both NF1 and BEST1 gene mutations.
An 8-year-old female patient with café-au-lait spots, freckling on skin presented to our ophthalmology clinic for routine ophthalmological examination. Her best corrected visual acuity (BCVA) was 20/20 in both eyes. Slit-lamp examination of both eyes revealed few yellowish-brown dome-shaped Lisch nodules over the iris surface. Fundus examination was notable for bilateral confluent yellowish subretinal deposits at macula, few yellow flecks at temporal retina, and cup-to-disc ratio of 0.2. Optical coherence tomography (OCT) revealed subretinal fluid (SRF) involving the fovea, elongated photoreceptor outer segments and mild intraretinal fluid (IRF) at bilateral macula. Fundus autofluorescence demonstrated hyperautofluorescence in the area corresponding to the subretinal deposits. Whole-exome sequencing and Sanger sequencing were used to investigate genetic mutation in the patient and her parents. A BEST1 gene heterozygous missense c.604 C > T (p.Arg202Trp) was identified in the patient and her mother. Also, the patient carries an NF1 nonsense mutation c.6637 C > T (p.Gln2213*) with the mosaic generalized phenotype. There were no visual impairments or obvious neurological, musculoskeletal, behavioral or other symptoms in this patient, so she was managed conservatively and advised to follow up regularly for a long time.
ARB and NF1, which are caused by two different pathogenic gene mutations, have rarely coexisted in the same patient. The discovery of pathogenic gene mutations may play a crucial role in more accurate diagnostics and genetic consultations for individuals and their families.
神经纤维瘤病 1 型（NF1）是一种多系统遗传疾病，可能影响身体的多个系统。常染色体隐性 Bestrophinopathy（ARB）是一种由常染色体隐性 Bestrophin 1（BEST1）基因突变引起的罕见视网膜营养不良。到目前为止，我们尚未检索到同一患者同时患有 NF1 和 BEST1 基因突变的病例报告。
一名 8 岁女性患者，有咖啡牛奶斑和皮肤雀斑，因常规眼科检查就诊于我院眼科门诊。她的最佳矫正视力（BCVA）双眼均为 20/20。双眼裂隙灯检查显示虹膜表面有几个黄褐色的圆顶状 Lisch 结节。眼底检查显示双眼黄斑区有融合的黄白色视网膜下沉积物，颞侧视网膜有几个黄色斑点，杯盘比为 0.2。光学相干断层扫描（OCT）显示黄斑区有视网膜下积液（SRF），累及黄斑，双侧光感受器外节拉长，黄斑区有轻度视网膜内液（IRF）。眼底自发荧光显示与视网膜下沉积物相对应的区域有高自发荧光。对患者及其父母进行全外显子组测序和 Sanger 测序，以检测基因突变。患者及其母亲均发现 BEST1 基因杂合错义突变 c.604C>T（p.Arg202Trp）。此外，患者还携带 NF1 无义突变 c.6637C>T（p.Gln2213*），表现为马赛克全身表型。该患者无视力损害或明显的神经、肌肉骨骼、行为或其他症状，因此予以保守治疗，并建议长期定期随访。
ARB 和 NF1 由两种不同的致病基因突变引起，在同一患者中很少同时存在。致病基因突变的发现可能对个体及其家属的更准确诊断和遗传咨询起到关键作用。
