Abu-Amero Khaled K, Kondkar Altaf A, Khan Arif O
Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, 60612, USA.
BMC Res Notes. 2017 Nov 6;10(1):562. doi: 10.1186/s13104-017-2888-y.
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is known to be caused by mutations in KIF21A or TUBB3 or other known genes (SALL4, CHN1, HOXA1). However, affected children may harbor other genetic defects. Therefore, a candidate gene analysis (KIF21A, TUBB3 SALL4, CHN1, HOXA1) and a high-resolution array comparative genomic hybridization (arrayCGH) was performed in two unrelated children with sporadic CFEOM1.
Two unrelated Saudi patients did not have any mutation(s) after sequencing the full coding regions of SALL4, CHN1, HOXA1, and TUBB3 genes; and exons 8, 20, and 21 of the KIF21A gene. However, arrayCGH revealed a 3.17 Kb deletion at chromosome 8p22 with copy number state equal to 1, indicating a heterozygous deletion. This deletion was absent in proband's mother or father or 220 unrelated healthy individuals of similar ethnicity. The deletion encompassed only one functional gene, GRHL2, which encodes a transcription factor. In humans, defects in this gene are a cause of non-syndromic sensorineural deafness, autosomal dominant type 28 (DFNA28). We speculate that GRHL2 gene may have a role in orbital innervations and the defect in this gene (deletion) may be related to the CFEOM1 phenotype in these two children.
已知先天性眼外肌纤维化1型（CFEOM1）由KIF21A或TUBB3或其他已知基因（SALL4、CHN1、HOXA1）的突变引起。然而，受影响的儿童可能存在其他基因缺陷。因此，对两名散发性CFEOM1的无关儿童进行了候选基因分析（KIF21A、TUBB3、SALL4、CHN1、HOXA1）和高分辨率阵列比较基因组杂交（arrayCGH）。
两名无关的沙特患者在对SALL4、CHN1、HOXA1和TUBB3基因的完整编码区以及KIF21A基因的第8、20和21外显子进行测序后未发现任何突变。然而，阵列CGH显示8号染色体p22处有一个3.17 Kb的缺失，拷贝数状态为1，表明为杂合缺失。该缺失在先证者的母亲或父亲或220名种族相似的无关健康个体中不存在。该缺失仅包含一个功能基因GRHL2，其编码一种转录因子。在人类中，该基因的缺陷是常染色体显性28型非综合征性感音神经性耳聋（DFNA28）的病因。我们推测GRHL2基因可能在眼眶神经支配中起作用，该基因的缺陷（缺失）可能与这两名儿童的CFEOM1表型有关。
