Bredrup Cecilie, Johansson Stefan, Bindoff Laurence A, Sztromwasser Pawel, Kråkenes Jostein, Mellgren Anne E C, Brurås Kari R, Lind Ola, Boman Helge, Knappskog Per M, Rødahl Eyvind
Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
Am J Ophthalmol. 2015 May;159(5):973-9.e2. doi: 10.1016/j.ajo.2015.01.021. Epub 2015 Jan 26.
To investigate the ocular and neurologic manifestations, and to identify the causative mutation in a family with an excavated optic disc anomaly, high myopia, enlarged axial lengths, and abnormal visual evoked response (VER).
Prospective observational case series with whole exome sequencing.
Institutional study of 8 family members from 3 generations. Clinical examination included visual field examination, optical coherence tomography, axial length measurement, audiometry, visual evoked response (VER), orbital and cerebral magnetic resonance imaging (MRI), and renal ultrasound. DNA was analyzed by whole exome sequencing and Sanger sequencing. Main outcome measures were clinical and radiological findings, and DNA sequence data.
Three affected family members, a father and his 2 daughters, were examined. The parents and siblings of the father were healthy. Affected individuals presented with excavated optic discs, high myopia (-1.00 to -16.00 diopters), and increased axial lengths. Reduced visual acuity (0.05-0.8) and decreased sensitivity on visual field examination were observed. VER revealed prolonged latency times. Affected eyes appeared ovoid on MRI and the father had thin optic nerves. Exome sequencing revealed that the father was heterozygous for a de novo 5 bp deletion in MYCBP2, c.5906_5910del; p.Glu1969Valfs*26. The same mutation was found in his 2 affected daughters, but not in his parents or siblings, or in public databases.
We describe a distinct excavated optic disc anomaly associated with high myopia and increased axial length. The condition appears to follow an autosomal dominant pattern and segregate with a deletion in MYCBP2. We suggest naming this entity high myopia-excavated optic disc anomaly.
研究一个患有视盘凹陷异常、高度近视、眼轴长度增加和视觉诱发电位（VER）异常的家系的眼部和神经学表现，并鉴定致病突变。
采用全外显子组测序的前瞻性观察性病例系列研究。
对来自3代的8名家庭成员进行机构性研究。临床检查包括视野检查、光学相干断层扫描、眼轴长度测量、听力测定、视觉诱发电位（VER）、眼眶和脑部磁共振成像（MRI）以及肾脏超声检查。通过全外显子组测序和桑格测序对DNA进行分析。主要观察指标为临床和影像学检查结果以及DNA序列数据。
检查了3名受影响的家庭成员，一名父亲及其2个女儿。父亲的父母和兄弟姐妹均健康。受影响的个体表现为视盘凹陷、高度近视（-1.00至-16.00屈光度）以及眼轴长度增加。观察到视力下降（0.05 - 0.8）和视野检查时敏感度降低。VER显示潜伏期延长。MRI显示患眼呈椭圆形，父亲的视神经较细。外显子组测序显示，父亲在MYCBP2基因中存在一个新发的5bp缺失，c.5906_5910del；p.Glu1969Valfs*26，为杂合子。在他的2名受影响的女儿中也发现了相同的突变，但在其父母、兄弟姐妹或公共数据库中未发现。
我们描述了一种与高度近视和眼轴长度增加相关的独特的视盘凹陷异常。该病症似乎遵循常染色体显性遗传模式，并与MYCBP2基因的缺失相关。我们建议将这种病症命名为高度近视 - 视盘凹陷异常。
