Mackenna E Schouw, Claudia A L Ruivenkamp, Tamara T Koopmann, Gijs W E Santen, Peter G J Nikkels, Karin van der Tuin
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引用次数: 0
Abstract
Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.2451 + 77C > T in intron 35 of COL1A1, which resulted in aberrant splicing and the in-frame addition of 75 nucleotides into the mRNA. These patients highlight the importance of considering deep intronic variants in type 1 collagen genes in patients with high suspicion of OI, which may be missed with conventional genetic analysis.
期刊介绍：
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .
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