Ahmad Almatrafi1, Fatima Alfadhli2, Yasir Naseem Khan3, Sibtain Afzal4, Jamil A Hashmi5, Anhar Ullah6, Alia M Albalawi5, Sulman Basit5. 1. 1 College of Science, Taibah University, Almadinah Almunawwarah, Saudi Arabia. 2. 2 Department of Genetic Diseases, King Abdulla Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah, Saudi Arabia. 3. 3 Department of Anatomy, Al-Rayan Medical College, Almadinah Almunawwarah, Saudi Arabia. 4. 4 Department of Pediatrics, Asthma Research Chair and Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 5. 5 Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Saudi Arabia. 6. 6 Cardiac Sciences Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Abstract
Objective:Heterozygous pathogenic variants in the COL2A1 gene result in several clinical features including impaired skeletal growth, ocular and otolaryngological abnormalities. Missense mutations in the triple helical region of the COL2A1 protein have been associated with lethal spondyloepiphyseal dysplasia (SED). In this study, we aimed to identify the underlying cause of a case of SED congenita (SEDC) in a 27-month-old child. Materials and Methods: A patient who was diagnosed initially with osteochondrodysplasia underwent a detailed clinical and radiological examination to obtain a conclusive diagnosis. The patient did not show any clinical features of hypochondrogenesis. Whole exome sequencing of the COL2A1 gene was carried out to identify the underlying genetic cause of the disorder. Results: Variant annotation and filtration detected a heterozygous missense mutation c.1357G>A (p.G453S) in the exon 21 of the COL2A1 gene of the proband which was confirmed by Sanger sequencing. Neither parent carried the mvariant suggesting this was a new mutation. Conclusion: The COL2A1 mutation (c.1357G>A), identified in this case, results in more mild phenotype than other missense mutations in exon 21 which are known to cause lethal hypochondrogenesis. We showed, for the first time, that a missense mutation (p.G453S) in the triple helical region of the alpha 1 (II) chain of the COL2A1 protein underlies SEDC and is not always lethal.
Objective:Heterozygous pathogenic variants in the COL2A1 gene result in several clinical features including impaired skeletal growth, ocular and otolaryngological abnormalities. Missense mutations in the triple helical region of the COL2A1 protein have been associated with lethal spondyloepiphyseal dysplasia (SED). In this study, we aimed to identify the underlying cause of a case of SED congenita (SEDC) in a 27-month-old child. Materials and Methods: A patient who was diagnosed initially with osteochondrodysplasia underwent a detailed clinical and radiological examination to obtain a conclusive diagnosis. The patient did not show any clinical features of hypochondrogenesis. Whole exome sequencing of the COL2A1 gene was carried out to identify the underlying genetic cause of the disorder. Results: Variant annotation and filtration detected a heterozygous missense mutation c.1357G>A (p.G453S) in the exon 21 of the COL2A1 gene of the proband which was confirmed by Sanger sequencing. Neither parent carried the mvariant suggesting this was a new mutation. Conclusion: The COL2A1 mutation (c.1357G>A), identified in this case, results in more mild phenotype than other missense mutations in exon 21 which are known to cause lethal hypochondrogenesis. We showed, for the first time, that a missense mutation (p.G453S) in the triple helical region of the alpha 1 (II) chain of the COL2A1 protein underlies SEDC and is not always lethal.
Authors: Syed Ashraf Uddin; Nicole Cesarato; Aytaj Humbatova; Axel Schmidt; Fazal urRehman; Muhammad Naeem; Abdul Samad Tareen; Sabrina Wolf; Muhammad Anwar Panezai; Holger Thiele; Abdul Wali; Regina Fölster-Holst; Sulman Basit; Muhammad Ayub; Regina C Betz Journal: Acta Derm Venereol Date: 2020-09-30 Impact factor: 3.875