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IPSC reprogramming of two patients with spondyloepiphyseal dysplasia congenita (SEDC).

ABSTRACT: Spondyloepiphyseal dysplasia congenita (SEDC) is a severe non-lethal type 2 collagenopathy caused by pathogenic variants in the COL2A1 gene, which encodes the alpha-1 chain of type II collagen. SEDC is clinically characterized by severe short stature, degenerative joint disease, hearing impairment, orofacial anomalies and ocular manifestations. To study and therapeutically target the underlying disease mechanisms, human iPSC-chondrocytes are considered highly suitable as they have been shown to exhibit several key features of skeletal dysplasias. Prior to creating iPSC-chondrocytes, peripheral blood mononuclear cells of two male SEDC patients, carrying the p.Gly1107Arg and p.Gly408Asp pathogenic variants, respectively, were successfully reprogrammed into iPSCs using the CytoTune™-iPS 2.0 Sendai Kit (Invitrogen).

SUBMITTER: De Kinderen P

PROVIDER: S-EPMC10240565 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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IPSC reprogramming of two patients with spondyloepiphyseal dysplasia congenita (SEDC).

De Kinderen Pauline P Rabaut Laura L Perik Melanie H A M MHAM Peeters Silke S Ponsaerts Peter P Loeys Bart B Mortier Geert G Meester Josephina A N JAN Verstraeten Aline A

Stem cell research 20230321

Spondyloepiphyseal dysplasia congenita (SEDC) is a severe non-lethal type 2 collagenopathy caused by pathogenic variants in the COL2A1 gene, which encodes the alpha-1 chain of type II collagen. SEDC is clinically characterized by severe short stature, degenerative joint disease, hearing impairment, orofacial anomalies and ocular manifestations. To study and therapeutically target the underlying disease mechanisms, human iPSC-chondrocytes are considered highly suitable as they have been shown to ...[more]

PMID: 36966641

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Novel COL2A1 variants in Japanese patients with spondyloepiphyseal dysplasia congenita.

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Novel variants in COL2A1 causing rare spondyloepiphyseal dysplasia congenita.

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A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis.

Project description:UNLABELLED:A missense mutation in the mouse Col2a1 gene has been discovered, resulting in a mouse phenotype with similarities to human spondyloepiphyseal dysplasia (SED) congenita. In addition, SED patients have been identified with a similar molecular mutation in human COL2A1. This mouse model offers a useful tool for molecular and biological studies of bone development and pathology. INTRODUCTION:A new mouse autosomal recessive mutation has been discovered and named spondyloepiphyseal dysplasia congenita (gene symbol sedc). MATERIALS AND METHODS:Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora, and tibias, plus retinoschisis and hearing loss. The mutation was mapped to Chr15, and Col2a1 was identified as a candidate gene. RESULTS:Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417. Two human patients with spondyloepiphyseal dysplasia (SED) congenita have been reported with the same amino acid substitution at position 789 in the human COL2A1 gene. CONCLUSIONS:Thus, sedc/sedc mice provide a valuable model of human SED congenita with molecular and phenotypic homology. Further biochemical analyses, molecular modeling, and cell culture studies using sedc/sedc mice could provide insight into mechanisms of skeletal development dependent on Col2a1 and its role in fibril formation and cartilage template organization.

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Identification of a Novel Mutation in the COL2A1 Gene in a Chinese Family with Spondyloepiphyseal Dysplasia Congenita.

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Identification of an Autosomal Dominant Mutation in the COL2A1 Gene Leading to Spondyloepiphyseal Dysplasia Congenita in a Greek Family.

Project description:A boy and his father with severe short stature, progressively evolving body asymmetry, and skeletal abnormalities are presented. A next-generation sequencing exome study was performed, and the patient was found heterozygous for the c.1609G>A (p.Gly537Ser) mutation in the COL2A1 gene. This mutation is considered a pathogenic variant and has been previously registered in the Human Gene Mutation Database (HGMD) in association with spondyloepiphyseal dysplasia (accession: CM052184). It has been described in a patient as a sporadic case and resulted in a severe phenotype. Segregation studies, in order to determine the inheritance pattern, identified the same mutation in our patient's father. The variant was transmitted in an autosomal dominant pattern. In conclusion, we describe a patient with hereditary spondyloepiphyseal dysplasia congenita, caused by a c.1609G_A (p.Gly537Ser) mutation in the COL2A1 gene, which resulted in a milder phenotype.

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