A case of Culler-Jones syndrome caused by a novel mutation of GLI2 gene and literature review

In 1984, Culler and Jones already described the characteristics of Culler-Jones syndrome: postaxial polydactyly, multiple pituitary hormone deficiencies, dysmorphic facial features and autosomal dominant pattern of inheritance. The disease's clinical phenomenology and gene mutation sites have been continuously expanded as more cases have been reported globally. We report a case of a child with anosmia, partial GH deficiency, hypogonadotropic hypogonadism and secondary low bone mass, in which high-throughput gene sequencing suggested a missense mutation in GLI2 gene c.527A>G (p.Tyr176Cys). This mutation site has not yet been documented in any published works. On the one hand, we anticipate that our discovery will spark researchers' interest in this novel site and lead to the development of functional testing for this gene. On the other hand, we hope to broaden clinicians' knowledge of diseases related to growth and development delays in children, so that patients with similar manifestations can be distinguished carefully with Culler-Jones syndrome. In conclusion, this case report can not only aid in fundamental scientific research and provide direction for basic experiments, but it can also widen clinicians' perspectives on diagnosis and treatment, enabling more children with uncommon disorders to obtain early diagnosis and treatment.

1984年，Culler与Jones即已系统阐述Culler-Jones综合征（Culler-Jones syndrome）的临床特征：轴后多指畸形、多种垂体激素缺乏、面部畸形体征及常染色体显性遗传模式。随着全球范围内陆续报道更多病例，该疾病的临床表型与基因突变位点研究亦不断得到拓展。本次我们报道1例以嗅觉缺失、生长激素（Growth Hormone, GH）部分缺乏、促性腺激素缺乏性性腺功能减退症及继发性骨量减少为表现的患儿，经高通量基因测序（high-throughput gene sequencing）检测发现其GLI2基因（GLI2 gene）存在c.527A>G（p.Tyr176Cys）错义突变。该突变位点迄今尚未见任何已发表文献记载。一方面，我们期望本研究发现能够激发研究者对该新型突变位点的探索兴趣，并推动针对该基因的功能检测技术开发；另一方面，我们希望拓宽临床医师对儿童生长发育延迟相关疾病的认知水平，以便能够将表现相似的患者与Culler-Jones综合征进行精准鉴别。综上，本病例报告不仅可为基础科学研究提供方向并指导基础实验开展，同时也能拓宽临床医师的诊疗视野，使更多罕见疾病患儿能够获得早期诊断与规范治疗。