Hospital Universitário Clemente de Faria, Universidade Estadual de Montes Claros, Montes Claros, MG, Brazil.
Faculdade de Medicina, Universidade Estadual de Montes Claros, Montes Claros, MG, Brazil.
Arq Bras Oftalmol. 2024 Nov 22;88(3). doi: 10.5935/0004-2749.2023-0115. eCollection 2024.
To evaluate the presence of congenital hypertrophy of the retinal pigment epithelium in a large family affected by familial adenomatous polyposis and identify the causative mutation in the adenomatous polyposis coli gene. Thus, we aimed to determine the significance of congenital hypertrophy of the retinal pigment epithelium as a phenotypic marker of the disease.
A family consisting of 95 individuals was evaluated. Among these, 45 individuals were randomly selected by convenience sampling method to undergo ophthalmological evaluation. A funduscopic exam, including slit lamp and indirect ophthalmoscopy, were performed in the selected patients. In those with retinal lesions, a retinography was obtained. The adenomatous polyposis coli gene was sequenced in one affected family member to identify the pathogenic mutation. Once the variant was identified, six undiagnosed family members were tested for the mutation via capillary electrophoresis sequencing.
Congenital hypertrophy of the retinal pigment epithelium was observed in 13 (28.9%) of the 45 individuals evaluated. Of these, nine patients were confirmed to have familial adenomatous polyposis (via colonoscopy or molecular testing). However, four patients had not been investigated. Of the 32 (71.1%) family members without the lesion, 14 did not have familial adenomatous polyposis and 18 were yet to be evaluated. The lesions were bilaterally present and exhibited a peculiar fish-tail shape in all the evaluated individuals. Adenomatous polyposis coli gene sequencing revealed a pathogenic variant c.4031del. (Ser1344*), in heterozygosity (49.27%), in exon 16.
The study findings confirmed the significance of congenital hypertrophy of the retinal pigment epithelium as a phenotypic marker for familial adenomatous polyposis. Furthermore, it is an effective first-line screening method for at risk family members of such patients. The novel mutation identified in our study participants, which is yet to be described in the literature, causes an aggressive form of the disease.
评估一个受家族性腺瘤性息肉病影响的大家庭中先天性视网膜色素上皮肥大的存在，并确定腺瘤性息肉病结肠基因中的致病突变。因此，我们旨在确定先天性视网膜色素上皮肥大作为疾病表型标志物的意义。
评估了一个由 95 人组成的家庭。其中，通过方便抽样法随机选择 45 人进行眼科评估。在选定的患者中进行眼底检查，包括裂隙灯和间接检眼镜。在有视网膜病变的患者中，进行视网膜摄影。对一个受影响的家庭成员进行腺瘤性息肉病结肠基因测序，以确定致病突变。一旦确定了变体，通过毛细管电泳测序对六个未确诊的家族成员进行突变测试。
在评估的 45 人中，观察到 13 人（28.9%）存在先天性视网膜色素上皮肥大。其中，9 名患者经结肠镜检查或分子检测证实患有家族性腺瘤性息肉病。然而，有 4 名患者未进行调查。在 32 名（71.1%）无病变的家族成员中，14 名没有家族性腺瘤性息肉病，18 名尚未进行评估。病变是双侧的，在所有评估的个体中都表现出一种奇特的鱼尾状。腺瘤性息肉病结肠基因测序显示，外显子 16 中的 c.4031del.（Ser1344*）杂合性致病性变体（49.27%）。
研究结果证实了先天性视网膜色素上皮肥大作为家族性腺瘤性息肉病的表型标志物的意义。此外，它是此类患者高危家族成员的有效一线筛查方法。在我们的研究参与者中发现的新突变，尚未在文献中描述，导致疾病的侵袭性形式。
