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Background: FERM domain-containing protein 4A (FRMD4A) is a scaffolding protein previously proposed to be critical in the regulation of cell polarity in neurons and implicated in human intellectual development.Case Presentation: We report a case of a 3-year-old boy with corpus callosum anomaly, relative macrocephaly, ataxia, and unexplained global developmental delay. Here, compound heterozygous missense mutations in the FRMD4A gene [c.1830G>A, p.(Met610Ile) and c.2973G>C, p.(Gln991His)] were identified in the proband, and subsequent familial segregation showed that each parent had transmitted a mutation.Conclusions: Our results have confirmed the associations of mutations in the FRMD4A gene with intellectual development and indicated that for patients with unexplained global developmental delay, the FRMD4A gene should be included in the analysis of whole exome sequencing data, which can contribute to the identification of more patients affected by this severe phenotypic spectrum.

Background: Osteogenesis imperfecta (OI) is a clinical and genetic disorder that results in bone fragility, blue sclerae and dentineogenesis imperfecta (DGI), which is mainly caused by a mutation in the COL1A1 or COL1A2 genes, which encode type I procollagen.Case Report: A missense mutation (c.1463G > C) in exon 22 of the COL1A1 gene was found using whole-exome sequencing. However, the cases reported herein only exhibited a clinical DGI-I phenotype. There were no cases of bone disease or any other common abnormal symptom caused by a COL1A1 mutation. In addition, the ultrastructural analysis of the tooth affected with non-syndromic DGI-I showed that the abnormal dentine was accompanied by the disruption of odontoblast polarization, a reduced number of odontoblasts, a reduction in hardness and elasticity, and the loss of dentinal tubules, suggesting a severe developmental disorder. We also investigated the odontoblast differentiation ability using dental pulp stem cells (DPSCs) that were isolated from a patient with DGI-I and cultured. Stem cells isolated from patients with DGI-I are important to elucidate their pathogenesis and underlying mechanisms to develop regenerative therapies.Conclusion: This study can provide new insights into the phenotype-genotype association in collagen-associated diseases and improve the clinical diagnosis of OI/DGI-I.