Expanded phenotypes and pathogenesis of geleophysic dysplasia 3 resulted from a de novo LTBP3 mutation: A case report.

RATIONALE: The aim of this study is to investigate the de novo mutation and clinical features of latent transforming growth factor-beta-binding protein 3 (LTBP3) gene-associated geleophysic dysplasia 3, and possible mechanisms of action.

PATIENT CONCERNS: A nonconsanguineous couple was recruited for this study due to the presence of intrauterine growth restriction. The pregnant woman and her elder daughter presented with skeletal abnormalities with diabetes. The pregnant woman underwent amniocentesis for cytogenetic analysis and copy number variation sequencing. Furthermore, we employed a combination of pedigree whole exome sequencing and bioinformatics analysis to predict the effects of mutations.

DIAGNOSES: The results of karyotyping and copy number variation sequencing were normal. And the whole exome sequencing results indicated that the family carried a de novo mutation c.852_853insAGG (p.L284_P285insR) in the LTBP3 gene (NM_001130144.3) inherited from the mother. The results of bioinformatics prediction demonstrated the mutation influenced the stability of the LTBP3 gene, thereby enhanced the transforming growth factor β signaling pathways.

INTERVENTIONS: The couple terminated the pregnancy after comprehensive consideration.

OUTCOMES: A de novo non-frameshift mutation of the LTBP3 gene might enhance the transforming growth factor β signaling pathways, thereby leading to geleophysic dysplasia 3.

LESSONS: As a rare multi-system musculoskeletal disorder, geleophysic dysplasia 3 necessitates early prenatal diagnosis and multidisciplinary consultation in order to facilitate further diagnosis and evaluation of the patient and the fetus.