Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism

Abstract

Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused by mutations in the () gene with classic and well-recognizable clinical findings. However, parents affected with a mild phenotype, probably with somatic mosaicism, can generate offspring with a much more severe phenotype of AOI. In the present report, we describe a female newborn with classic AOI leading to early neonatal death, whose diagnostic was based on prenatal radiological findings and on the physical examination of the father. Since her father had limb deformities and corporal asymmetry, suggesting somatic mosaicism, his biological samples were analyzed through a gene panel for skeletal dysplasias. A missense mutation not previously described in the literature was detected in the gene, affecting ∼ 20% of the evaluated cells and, therefore, confirming the diagnosis of mosaic AOI in the father. The molecular analysis of the father was crucial to suggest the diagnosis of AOI in the newborn, since she died early and there were no biological samples available.

Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study

“…FLNB binds to actin to form the branching network of filaments that makes up the cytoskeleton, and is involved in the development of the skeleton before birth [36]. Missense actin mutations in FLNB leading to atelosteogenesis type I [37] and lethal skeletal dysplasia or inhibition of ERK/MMP-2 and MMP-9 pathways that are critical for trophoblast invasion [38], may be possible mechanisms of potentially lethal de novo FLNB SNVs in stillbirth etiology [39]. Similarly, MYO1C (Myosin isoform C) encodes actin-based motor molecules involved in insulin and VEGFA-VEGFR2 signaling pathways and chromatin remodeling.…”