Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University, 72076, Tübingen, Germany.
Genome Research Division, Human Genetics Department, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands.
Orphanet J Rare Dis. 2022 Mar 3;17(1):97. doi: 10.1186/s13023-022-02244-6.
Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date.
Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3. Further, we have collected COL9A3 genotype-phenotype associations from the literature.
Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.
成骨不全症（STL）是一种罕见的、临床和分子异质性结缔组织疾病。发生在多种基因中的致病变异导致 STL，主要以常染色体显性遗传方式遗传。常染色体隐性 STL 极为罕见，迄今为止仅报道了四组具有双等位基因 COL9A3 变异的家系。
在这里，我们报告了三个无关的临床诊断为 STL 的家系，这些家系携带有不同的新型 COL9A3 双等位基因功能丧失变异。此外，我们还从文献中收集了 COL9A3 基因型-表型相关性。
我们的报告大大扩展了常染色体隐性 STL 的分子遗传学和临床基础，并提供了关于等位基因 COL9A3 疾病的概述。
