AUTHOR=Shen Yingxiao , Xu Xiaoqin , Chen Jiansong , Wang Jingjing , Dong Guanping , Huang Ke , Fu Junfen , Wu Dingwen , Wu Wei TITLE=De novo 11q13.3q13.4 deletion in a patient with Fanconi renotubular syndrome and intellectual disability: Case report and review of literature JOURNAL=Frontiers in Pediatrics VOLUME=11 YEAR=2023 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1097062 DOI=10.3389/fped.2023.1097062 ISSN=2296-2360 ABSTRACT=Objective

To explore the genetic etiology of a child with facial dysmorphia, developmental delay, intellectual disability, Fanconi renotubular syndrome, and Chiari malformations.

Materials and methods

Whole exome sequencing (WES), Copy number variation sequencing (CNV-seq), and mitochondrial gene detection (Long-PCR + NGS) were applied to detect possible pathogenic mutations and chromosomal copy number variations (CNVs), together with databases and literature reviews to clarify the pathological significance of the candidate mutations.

Results

The WES revealed a 2.10 Mb interstitial deletion from 11q13.3 to 11q13.4, which was later confirmed by CNV-seq involving 11 OMIM genes, among which SHANK2, DHCR7, NADSYN1, FADD, NUMA1, IL18BP, ANO1, and FGF3 are disease-causing. The mitochondrial gene shows no variations.

Conclusion

The child has carried a de novo 11q13.3q13.4 microdeletion, in which SHANK2 genes may be the key gene responsible for the phenotype of intellectual disability. The renal manifestation of the child, which can be diagnosed as Fanconi renotubular syndrome, has an unknown cause but may result from the effect of the ANO1 gene. This case adds a new phenotype to the deletion of this region.