Open AccessGnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran
Author(s) -
Yassaee Vahid Reza,
Khojasteh Arash,
HashemiGorji Farzad,
Sadeghi Hossein,
Safiaghdam Hannaneh,
Mirfakhraie Reza
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.2004
Subject(s) - sanger sequencing , proband , exome sequencing , genetics , dna sequencing , genetic counseling , dysplasia , genetic testing , tooth disease , medicine , in silico , bioinformatics , biology , mutation , gene
Background 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. Methods 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. Results 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. Conclusion In summary, our investigation identified a novel pathogenic variant in the ANO5, responsible for gnathodiaphyseal dysplasia in a large Iranian family. Therefore, based on the present study, this variant can be helpful for diagnosis and effective management of GDD patients.