PDF(Pubmed)
Abstract：
UNASSIGNED: To clinically and molecularly study a newly found family with North Carolina macular dystrophy (NCMD/MCDR1) from Mexico.
UNASSIGNED: This retrospective study comprised 6 members of a 3-generation Mexican family with NCMD. Clinical ophthalmic examinations, including fundus imaging, spectral-domain optical coherence tomography, electroretinography, and electrooculography, were performed. Genotyping with polymorphic markers in the MCDR1 region was performed to determine haplotypes. Whole-genome sequencing (WGS) was performed followed by variant filtering and copy number variant analysis.
UNASSIGNED: Four subjects from 3 generations were found to have macular abnormalities. The proband presented with lifelong bilateral vision impairment with bilaterally symmetric vitelliform Best disease-like appearing macular lesions. Her 2 children had bilateral large macular coloboma-like malformations, consistent with autosomal dominant NCMD. The 80-year-old mother of the proband had drusen-like lesions consistent with grade 1 NCMD. WGS and subsequent Sanger sequencing found a point mutation at chr6:99593030G>C (hg38) in the noncoding region of the DNase I site thought to be a regulatory element of the retinal transcription factor gene PRDM13. This mutation is the identical site/nucleotide as in the original NCMD family (#765) but is a guanine to cytosine change rather than a guanine to thymine mutation, as found in the original NCMD family.
UNASSIGNED: We report a new noncoding mutation at the same locus (chr6:99593030G>C) involving the same DNase I site regulating the retinal transcription factor gene PRDM13. This suggests that this site, chr6:99593030, is a mutational hotspot.
UNASSIGNED: This retrospective study comprised 6 members of a 3-generation Mexican family with NCMD. Clinical ophthalmic examinations, including fundus imaging, spectral-domain optical coherence tomography, electroretinography, and electrooculography, were performed. Genotyping with polymorphic markers in the MCDR1 region was performed to determine haplotypes. Whole-genome sequencing (WGS) was performed followed by variant filtering and copy number variant analysis.
UNASSIGNED: Four subjects from 3 generations were found to have macular abnormalities. The proband presented with lifelong bilateral vision impairment with bilaterally symmetric vitelliform Best disease-like appearing macular lesions. Her 2 children had bilateral large macular coloboma-like malformations, consistent with autosomal dominant NCMD. The 80-year-old mother of the proband had drusen-like lesions consistent with grade 1 NCMD. WGS and subsequent Sanger sequencing found a point mutation at chr6:99593030G>C (hg38) in the noncoding region of the DNase I site thought to be a regulatory element of the retinal transcription factor gene PRDM13. This mutation is the identical site/nucleotide as in the original NCMD family (#765) but is a guanine to cytosine change rather than a guanine to thymine mutation, as found in the original NCMD family.
UNASSIGNED: We report a new noncoding mutation at the same locus (chr6:99593030G>C) involving the same DNase I site regulating the retinal transcription factor gene PRDM13. This suggests that this site, chr6:99593030, is a mutational hotspot.
摘要：
■对来自墨西哥的一个新发现的北卡罗来纳州黄斑营养不良（NCMD/MCDR1）家族进行临床和分子研究。
■这项回顾性研究包括3代墨西哥NCMD家族的6名成员。临床眼科检查,包括眼底成像,谱域光学相干层析成像,视网膜电图,还有眼电图,被执行了。用MCDR1区域中的多态性标记进行基因分型以确定单倍型。进行全基因组测序(WGS),然后进行变体过滤和拷贝数变体分析。
■发现3代中的4名受试者患有黄斑异常。先证者表现为终身双侧视力障碍，双侧对称卵黄样最佳疾病样黄斑病变。她的两个孩子有双侧大黄斑缺损样畸形，与常染色体显性NCMD一致。先证者的80岁母亲患有玻璃疣样病变，符合1级NCMD。WGS和随后的Sanger测序在被认为是视网膜转录因子基因PRDM13的调节元件的DNaseI位点的非编码区中发现了chr6:99593030G>C(hg38)的点突变。这种突变是与原始NCMD家族（＃765）相同的位点/核苷酸，但是是鸟嘌呤到胞嘧啶的变化，而不是鸟嘌呤到胸腺嘧啶的突变，在最初的NCMD家族中发现。
■我们报告了在同一基因座（chr6：99593030G>C）的新非编码突变，涉及调节视网膜转录因子基因PRDM13的相同DNaseI位点。这表明这个网站，chr6:99593030，是一个突变热点。
■这项回顾性研究包括3代墨西哥NCMD家族的6名成员。临床眼科检查,包括眼底成像,谱域光学相干层析成像,视网膜电图,还有眼电图,被执行了。用MCDR1区域中的多态性标记进行基因分型以确定单倍型。进行全基因组测序(WGS),然后进行变体过滤和拷贝数变体分析。
■发现3代中的4名受试者患有黄斑异常。先证者表现为终身双侧视力障碍，双侧对称卵黄样最佳疾病样黄斑病变。她的两个孩子有双侧大黄斑缺损样畸形，与常染色体显性NCMD一致。先证者的80岁母亲患有玻璃疣样病变，符合1级NCMD。WGS和随后的Sanger测序在被认为是视网膜转录因子基因PRDM13的调节元件的DNaseI位点的非编码区中发现了chr6:99593030G>C(hg38)的点突变。这种突变是与原始NCMD家族（＃765）相同的位点/核苷酸，但是是鸟嘌呤到胞嘧啶的变化，而不是鸟嘌呤到胸腺嘧啶的突变，在最初的NCMD家族中发现。
■我们报告了在同一基因座（chr6：99593030G>C）的新非编码突变，涉及调节视网膜转录因子基因PRDM13的相同DNaseI位点。这表明这个网站，chr6:99593030，是一个突变热点。
