Cervantes Aleck E, Gee Katherine M, Whiting Martha F, Frausto Ricardo F, Aldave Anthony J
a Stein Eye Institute , David Geffen School of Medicine at UCLA , Los Angeles , CA , USA.
Ophthalmic Genet. 2018 Aug;39(4):419-424. doi: 10.1080/13816810.2018.1459736. Epub 2018 Apr 19.
To present the clinical and cytogenetic features of a previously unreported family with posterior amorphous corneal dystrophy (PACD) associated with a heterozygous deletion of the small leucine-rich proteoglycan (SRLP) genes on chromosome 12.
Clinical characterization was performed using slit lamp biomicroscopic and optical coherence tomography (OCT) imaging. Genomic DNA was collected from affected and unaffected family members, and a cytogenomic array was used to identify copy number variations (CNV) present in the PACD locus.
Three members of a Guatemalan family presented with clinical characteristics consistent with PACD: bilateral posterior stromal lamellar opacification, decreased corneal curvature, and iridocorneal adhesions. OCT imaging demonstrated decreased corneal thickness and hyperreflectivity of the posterior third of the corneal stroma. CNV analysis confirmed the presumed clinical diagnosis of PACD by revealing a 0.304 Mb heterozygous deletion in the PACD locus on chromosome 12 that included the four SLRP genes (KERA, LUM, DCN, and EPYC) deleted in each of the PACD families in which CNV analysis has been reported.
This is the first report of the OCT appearance of PACD and the second confirmation of a heterozygous deletion of chromosome 12q21.33 as the cause of PACD, highlighting the utility of array-based cytogenomics to confirm the suspected clinical diagnosis of PACD. As the smallest previously reported pathogenic deletion was 0.701 Mb, the 0.304-Mb deletion we report is the smallest identified to date and reduces the size of the PACD locus to 0.275 Mb.
呈现一个此前未报道过的家族的临床和细胞遗传学特征，该家族患有与12号染色体上富含亮氨酸的小分子蛋白聚糖（SRLP）基因杂合缺失相关的后部无定形角膜营养不良（PACD）。
使用裂隙灯生物显微镜和光学相干断层扫描（OCT）成像进行临床特征分析。从受影响和未受影响的家族成员中收集基因组DNA，并使用细胞基因组阵列来识别PACD基因座中存在的拷贝数变异（CNV）。
一个危地马拉家族的三名成员表现出与PACD一致的临床特征：双侧后基质层混浊、角膜曲率降低和虹膜角膜粘连。OCT成像显示角膜厚度降低以及角膜基质后三分之一的高反射性。CNV分析通过揭示12号染色体上PACD基因座中的0.304 Mb杂合缺失，证实了PACD的推测临床诊断，该缺失包括在已报道CNV分析的每个PACD家族中均被删除的四个SLRP基因（KERA、LUM、DCN和EPYC）。
这是关于PACD的OCT表现的首次报告，也是对12q21.33染色体杂合缺失作为PACD病因的第二次确认，突出了基于阵列的细胞基因组学在确认PACD疑似临床诊断中的作用。由于此前报道的最小致病缺失为0.701 Mb，我们报告的0.304 Mb缺失是迄今为止确定的最小缺失，并将PACD基因座大小缩小至0.275 Mb。
