Gnathodiaphyseal dysplasia (GDD) is an ultrarare autosomal dominant bone dysplasia characterized by cementoosseous lesions of the jawbones, bone fragility, frequent bone fractures at the young age, bowing of tubular bones, and diaphyseal sclerosis of long bones associated with generalized osteopenia. GDD is caused by point mutations in anoctamin‐5 ( ANO5) on chromosome 11p14.3. For the past few years, next generation sequencing (NGS) technology has facilitated the discovery of causative variants in genetically heterogeneous diseases.
In this study, exome sequencing (ES) was performed using the DNA sample of the proband. Family histories and clinical information were collected through comprehensive medical examination and genetic counseling.
ES results identified a heterozygous variant, NM_213599.3:c.1078T>C(p.Cys360Arg) in the ANO5 gene. Sanger sequencing was performed to confirm the detected pathogenic variant in DNA samples of the entire family (except deceased individuals), which segregated with the disease within the family. Finally, in silico analysis was applied to test the pathogenicity of the variant using various online software.
Gnathodiaphyseal dysplasia (GDD) is an ultrarare autosomal dominant bone dysplasia characterized by cementoosseous lesions of the jawbones, bone fragility, frequent bone fractures at the young age. In this study, Exome Sequencing results identified a heterozygous mutation, NM_213599.3:c.1078T>C(p.Cys360Arg) in the ANO5 confirmed by Sanger sequencing.