Research Centre for Medical Genetics, Moscow, Russian Federation.
Central Clinical Hospital of the Russian Academy of Sciences, Moscow, Russian Federation.
BMC Med Genomics. 2020 Sep 18;13(Suppl 8):130. doi: 10.1186/s12920-020-00790-1.
Because of the significant occurrence of "WAGR-region" deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patients with deletions and in the patients' parents as it reveals complex chromosomal rearrangements and the risk of having another affected child, as well as to provide prenatal and/or preimplantation diagnostics.
DNA samples were obtained from the proband (a 2-year-old boy) and his two healthy parents. Molecular analysis revealed a 977.065 kb deletion that removed loci of the ELP4, PAX6, and RCN1 genes but did not affect the coding sequence of the WT1 gene. The deletion occurred de novo on the paternal allele. The patient had normal karyotype 46,XY and a de novo pericentric inversion of chromosome 11, inv(11)(p13q14).
We confirmed the diagnosis of congenital aniridia at the molecular level. For the patient, the risk of developing Wilms' tumor is similar to that in the general population. The recurrence risk for sibs in the family is low, but considering the possibility of gonadal mosaicism, it is higher than in the general population.
由于在新发先天性无虹膜症突变中频繁出现“WAGR 区”缺失，因此对于所有散发的无虹膜症病例，DNA 诊断至关重要，因为其有助于早期诊断 WAGR 综合征。标准细胞遗传学核型研究是缺失患者及其父母分子诊断的必要步骤，因为它揭示了复杂的染色体重排以及生育另一个患病孩子的风险，并为产前和/或植入前诊断提供依据。
从先证者（一名 2 岁男孩）及其两名健康父母中获取 DNA 样本。分子分析显示了一个 977.065kb 的缺失，该缺失消除了 ELP4、PAX6 和 RCN1 基因的位点，但不影响 WT1 基因的编码序列。该缺失为父源性单亲二体遗传。患者的核型正常，为 46,XY，11 号染色体发生了新发性近端着丝粒倒位，inv(11)(p13q14)。
我们在分子水平上确认了先天性无虹膜症的诊断。对于该患者，患肾母细胞瘤的风险与一般人群相似。该家系中同胞的再发风险较低，但考虑到性腺嵌合的可能性，其风险高于一般人群。
