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Case Reports
. 2023 Apr;68(4):287-290.
doi: 10.1038/s10038-022-01104-2. Epub 2022 Dec 16.

Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis

Prajna Udupa  1 , Debasish Kumar Ghosh  1 , Neethukrishna Kausthubham  1 , Hitesh Shah  2 , Sandip Bartakke  3 , Ashwin Dalal  4 , Katta M Girisha  1 , Gandham SriLakshmi Bhavani  5
Affiliations
Case Reports

Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis

Prajna Udupa et al. J Hum Genet. 2023 Apr.

Abstract

Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder caused by impaired osteoclast activity. In this study, we describe a 4-year-old boy with increased bone density due to osteopetrosis, autosomal recessive 8. Using genome sequencing, we identified a large deletion in the 5'-untranslated region (UTR) of SNX10 (sorting nexin 10), where the regulatory region of this gene is located. This large deletion resulted in the absence of the SNX10 transcript and led to abnormal osteoclast activity. SNX10 is one of the nine genes known to cause ARO, shown to interact with V-ATPase (vacuolar type H( + )-ATPase), as it plays an important role in bone resorption. Our study highlights the importance of regulatory regions in the 5'-UTR of SNX10 for its expression while also demonstrating the importance of genome sequencing for detecting large deletion of the regulatory region of SNX10.

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Conflict of interest statement

The authors declare no competing interests. All the authors have read and approved the final paper.

Figures

Fig. 1
Fig. 1
A Pedigree of the 4-year-old boy born to a second degree consanguineously married couple. B Radiographs showing that the proband has large skull, frontal bossing and pectus carinatum. C–G Radiographs at 4 years of age showing - (C) increased bone density at the outer cortex of the skull, (D, E) increase in bone mineral density at epiphyses and metaphyses. Irregular bone mineral density was noted at diaphysis, (E, F) increased thickness of vertebrae showing “sandwich” appearance of the vertebral plates
Fig. 2
Fig. 2
A Schematic representation showing ~72 kb indel variant upstream of SNX10. Screen capture of the BAM files analysis using the Integrative Genomics Viewer for the SNX10 indel (g.26263639_26335651delinsCA) was found in the proband (B) Sanger chromatogram showing homozygous deletion and insertion of two nucleotides in the proband. parents are carriers of the identified variant
Fig. 3
Fig. 3
A Agarose gel electrophoretic separation of reverse transcriptase PCR (RT-PCR) amplicons encompassing exon 1 and 7 and exon 6 and 7 performed on cDNA samples of proband, carriers (parents) and control. Proband showed absence of SNX10 transcript in the exon 1–7 primer set but lesser amount of transcript was observed in the exon 6–7 primer set; GAPDH represents control. B Densitometric quantification of the DNA bands obtained from RT-PCR with primers for exon 6 and 7 of SNX10
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