Background: Osteogenesis imperfecta type XVII (OI17) (MIM#182120) have been described recently due to mutation in secreted protein, acidic, cysteine-rich (SPARC) gene located on 5q33.1.
Objective and hypotheses: Here we report a novel mutation in SPARC causing OI17.
Case: Two siblings presented to our clinic at the age of 10.3 and 0.5 years old. Parents were consanguineous. The older one was born with birth weight −2.5 SDS and had contracture in distal part of the extremities. Severe scoliosis and hypotonicity was noted in early infancy. His first fracture in long bones has been detected at the age of 3 years. He was diagnosed as OI and pamidronate therapy had been initiated. Several long bone fractures, deformities, joint hyperlaxity, blue sclerae and inguinal hernia operation was noted in the patient. He had no dentinogenesis imperfecta. His sister was born term via C/S with a BW of −1.2 SDS. She had congenital fractures, axial hypotonicity and blue sclerae. They both had gross motor developmental delay, the brotherhad mild conductive hearing loss. His lumbar DEXA Z-score was −0.2 under pamidronate therapy for 6 years. They have no nephrocalcinosis. Whole-exome sequencing was performed and in the SPARC gene, homozygosity for nonsense variant, c.160G>T,p.Glu54X was identified in both siblings. No other variants for known OI genes were detected. The parents without OI were heterozygous for c.160G>T and this mutation was not found in IGBAM in house exome database including 1013 samples. This mutation was confirmed by Sanger sequencing.
Conclusion: Here we described clinical characteristics of two siblings with recently describedOI17, new mutation in SPARC gene, which can be clinically classified as Sillence type 4.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology