Type 2 collagenopathies encompass a large group of chondrodysplasias ranging from the perinatally lethal achondrogenesis type 2 and hypochondrogenesis at the severe end of the spectrum to early-onset osteoarthritis with normal stature at the milder end of the spectrum. With the exception of a few reported cases, these dysplasias are predominantly caused by heterozygous variants in the COL2A1 gene and hence show an autosomal dominant inheritance pattern. Here we report on two siblings, originating from a consanguineous family, who presented with disproportionate short stature, ocular abnormalities, cleft palate and hearing impairment. The radiographic study showed signs of a spondyloepiphyseal dysplasia, compatible with a type 2 collagen disorder. Indeed, both siblings were homozygous for a c.3111+2T > Cp.(Glu1033Lysfs*5) splice site variant in the COL2A1 gene. cDNA analysis performed on skin fibroblasts from the affected sibs revealed the co-occurrence of the wild-type transcript and an aberrant splice product, the latter believed to be degraded by nonsense-mediated mRNA decay. The parents who were heterozygous for this variant were phenotypically normal. This paper confirms that type 2 collagenopathies can show an autosomal recessive inheritance.

2型胶原病包括大量的软骨发育不良，从2型围产期致死的软骨发育不全和频谱严重末端的软骨形成到频谱较温和末端具有正常身高的早发性骨关节炎。除少数报道的病例外，这些发育异常主要是由COL2A1基因的杂合变异引起的，因此显示出常染色体显性遗传模式。在这里，我们报道了两个来自近亲家庭的兄弟姐妹，他们的身材矮小，眼部异常，pa裂和听力障碍不成比例。影像学检查显示有脊柱骨赘发育不良的迹象，与2型胶原蛋白疾病相适应。实际上，两个兄弟姐妹都是纯合的，c.3111 + 2T> Cp。（Glu1 033Lysfs * 5）COL2A1基因的剪接位点变异。对来自患病同胞的皮肤成纤维细胞进行的cDNA分析显示，野生型转录本和异常剪接产物同时存在，后者被废话介导的mRNA降解所降解。该变体杂合的父母在表型上是正常的。本文证实了2型胶原病可以显示常染色体隐性遗传。