Dataset Information

Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran.

ABSTRACT:

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.

SUBMITTER: Yassaee VR

PROVIDER: S-EPMC9482395 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran.

Yassaee Vahid Reza VR Khojasteh Arash A Hashemi-Gorji Farzad F Sadeghi Hossein H Safiaghdam Hannaneh H Mirfakhraie Reza R

Molecular genetics & genomic medicine 20220627 9

<h4>Background</h4>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 ...[more]

PMID: 35758145

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Project description:BACKGROUND:Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked recessive inherited osteochondrodysplasia caused by mutations in the TRAPPC2 gene. It is clinically characterized by disproportionate short stature and early onset of degenerative osteoarthritis. Clinical diagnosis can be challenging due to the late-onset of the disease and lack of systemic metabolic abnomalites. Genetic diagnosis is critical in both early diagnosis and management of the disease. Here we reported a five-generation Chinese SEDT family and described the novel molecular findings. METHODS:Detailed family history and clinical data were collected. Genomic DNA was extracted from venous blood samples of family members. The exons of genes known to be associated with skeletal disorders were captured and deep sequenced. Variants were annotated by ANNOVAR and associated with multiple databases. Putative variants were confirmed by Sanger sequencing. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. RESULTS:The proband was a 27-year-old Chinese male who presented with short-trunk short stature and joint pain. His radiographs showed platyspondyly with posterior humping, narrow hip-joint surfaces, and pelvic osteosclerosis. A pedigree analysis of 5 generations with 6 affected males revealed an X-linked recessive mode of inheritance. Affected males were diagnosed as SEDT according to the clinical and radiological features. Next-generation sequencing identified a novel variant of c.216_217del in the exon 4 of TRAPPC2 gene in the proband and other affected males. This variant resulted in the shift of reading frame and early termination of protein translation (p.S73Gfs*15). The mother and maternal female relatives of the proband were heterozygous carriers of the same variant, while no variations were detected in this gene of his father and other unaffected males. Based on the ACMG criteria, the novel c.216_217del variant of the TRAPPC2 gene was the pathogenic variant of this SEDT family. CONCLUSION:In this study we identified the novel pathogenic variant of of c.216_217del in the gene of TRAPPC2 in this five-generation Chinese SEDT family. Our findings expand the clinical and molecular spectrum of SEDT and helps the genetic diagnosis of SEDT patients.

Dataset Information

Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran.

Background

Methods

Results

Conclusion

Publications

Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran.

Similar Datasets

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