Brizola Evelise, Gnoli Maria, Tremosini Morena, Nucci Paolo, Bargiacchi Sara, La Barbera Andrea, Giglio Sabrina, Sangiorgi Luca
Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Mol Genet Genomic Med. 2020 Sep;8(9):e1353. doi: 10.1002/mgg3.1353. Epub 2020 Jun 17.
Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients.
Herein, we report a case of an 8-year- old child with Stickler Syndrome, presenting with early-onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene.
A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing.
We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early-onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene-related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease.
斯-利二氏综合征是一种罕见的结缔组织疾病，具有临床和遗传异质性。临床表现高度可变，包括儿童期的中度至重度近视、听力丧失、面部畸形特征、腭裂和早期骨关节炎。COL2A1、COL11A1和COL11A2突变占常染色体显性斯-利二氏综合征的大多数，特别是在约10%至20%的斯-利二氏综合征患者中发现了COL11A1基因的杂合突变。
在此，我们报告一例8岁患有斯-利二氏综合征的儿童病例，该患儿在儿童期早期出现近视并伴有玻璃体异常、面部畸形特征，后期出现轻度听力丧失。为了确定潜在的遗传原因，对COL11A1基因进行了全外显子组测序。
通过全外显子组测序鉴定出COL11A1基因一个新的从头杂合剪接位点变异（NM_001854: c.1845 + 5G> C），该变异此前未被报道。
我们报告了一例患有斯-利二氏综合征的儿童中一个新的COL11A1突变，该患儿表现出眼异常早期发作和儿童后期轻度听力丧失的表型。我们的研究结果证实了该疾病表达的变异性，即使在同一基因相关疾病的情况下也是如此，从而有助于增进对这种罕见疾病临床和分子基础的认识。
