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Over-Representation of Recessive Osteogenesis Imperfecta in Asian Indian Children
Inusha Panigrahi1, Yousaf Qureshi1, Uwe Kornak2
1Genetic Metabolic Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Insights
Early onset osteogenesis imperfecta (OI) in Asian Indian families is linked to genetic variants. Next-generation sequencing identified pathogenic variants in SERPINF1 and CRTAP genes, impacting mobility and leading to fractures.
Area of Science:
- Genetics
- Pediatrics
- Medical Genetics
Background:
- Early onset osteogenesis imperfecta (OI) is a severe genetic disorder characterized by bone fragility.
- Key genes implicated include WNT1, SERPINF1, P3H1, CREB3L1, and CRTAP, with COL1A1 glycine substitutions also causing lethal forms.
- Clinical manifestations include decreased mobility, recurrent fractures, deformities, and early mortality.
Purpose of the Study:
- To report the genetic findings and clinical experience of early onset osteogenesis imperfecta in Asian Indian families.
- To identify specific genetic variants responsible for severe OI phenotypes in affected children.
Main Methods:
- Next-generation sequencing (NGS) was employed to identify genetic variants in patients with severe OI.
- Clinical data and family history were collected and analyzed.
Main Results:
- Two patients with pathogenic variants in the SERPINF1 gene were identified.
- Two patients with severe OI and antenatal fractures were found to have pathogenic variants in the CRTAP gene.
- Prenatal diagnosis was successfully performed using chorionic villus sampling.
Conclusions:
- Genetic variants in SERPINF1 and CRTAP are significant causes of severe early onset osteogenesis imperfecta in the studied Asian Indian population.
- NGS is a crucial tool for diagnosing OI and enabling genetic counseling and prenatal diagnosis.
- Early intervention, such as zoledronate therapy, may be beneficial for affected infants.
Abstract:
Several genes are implicated in the etiology of early onset osteogenesis imperfecta (OI). The various genes causing severe OI include WNT1 , SERPINF1 , P3H1 , CREB3L1 , and CRTAP , although glycine substitutions in COL1A1chains have also been predicted to cause perinatal lethal OI . Patients with early onset OI present decreased mobility, recurrent rib fractures, bony deformities, and chest infections that lead to an early death. We reported our experience in children with OI in Asian Indian families, which includes two patients with SERPINF1 pathogenic variants; and another two patients with severe OI and antenatal fractures caused by pathogenic variants in the CRTAP gene, identified by next generation sequencing (NGS). For one affected fetus, medical termination of pregnancy was done. The other baby was started on zoledronate therapy just after birth and is now 3 years old. Prenatal diagnosis was subsequently done on chorionic villus sample in the latter family.
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