Background Microcephaly and chorioretinopathy (MCCRP) is a rare neuro-ophthalmologic disorder that causes microcephaly and chorioretinopathy. In a recessive inheritance pattern, there are three types: MCCRP1; MCCRP2 and MCCRP3. MCCRP3 results from pathogenic variants in the tubulin-gamma complex-associated protein 4 (TUBGCP4) gene.

Materials and Methods This is a case report of a patient with a molecular diagnosis defined by mutations in the TUBGCP4 gene. Segregation analyses were carried out.

Results The molecular investigation found two heterozygous variants c.1380 G > A (p.Trp460*) a novel nonsense variant, and c.1746 G > T (p Leu582=) a synonymous variant in TUBGCP4. The clinical phenotype was characterized by microcephaly, microphthalmia, chorioretinopathy, a punched-out retinal appearance, dysmorphic facial features, decreased visual acuity, and learning difficulties. The clinical features were similar to those described previously in children with MCCRP3. The proband also had additional features including centripetal obesity, stretch marks, acanthosis nigricans, scoliosis, and hypercholesterolemia. These other features could be part of a ciliopathy syndrome.

Conclusions MCCRP2 caused by pathogenic variants in PLK4 is well established as a ciliopathy disease. The role of TUBGCP4 is not well established in the cilium physiology. MCCRP3 may be part of the ciliopathy spectrum.

背景技术小头畸形和脉络膜视网膜病（MCCRP）是一种罕见的神经眼科疾病，会引起小头畸形和脉络膜视网膜病。在隐性继承模式中，有三种类型：MCCRP1；MCCRP2和MCCRP3。MCCRP3是由微管蛋白-γ复杂相关蛋白4（TUBGCP4）基因中的致病性变异产生的。

材料和方法这是一例患者的病例报告，该患者通过TUBGCP4基因突变定义了分子诊断。进行了分离分析。

结果的分子调查发现了两个杂合变体c.1380 G> A（p.Trp460 *）一种新颖的无义变体，和c.1746 G> T（P Leu582 =）同义变体在TUBGCP4。临床表型的特征是小头畸形，小眼症，脉络膜视网膜病变，视网膜穿孔，面部畸形，视力下降和学习困难。其临床特征与先前描述的MCCRP3儿童相似。先证者还具有其他特征，包括向心型肥胖，妊娠纹，黑棘皮病，脊柱侧弯和高胆固醇血症。这些其他特征可能是睫状体综合症的一部分。

结论由PLK4的致病性变异引起的MCCRP2已被确定为一种纤毛病。TUBGCP4在纤毛生理中的作用尚不明确。MCCRP3可能是纤毛病谱的一部分。