Novel SNX13 Frameshift Variant in an Individual with Developmental Delay

Topic: Brain proteins, microglia and lab models

Recently, an increasing number of genes have been associated with global developmental delay (GDD) and intellectual disability (ID). The sorting nexin (SNX) protein family plays multiple roles in protein trafficking and intracellular signaling. SNXs have been reported to be associated with several disorders, including Alzheimer disease and Down syndrome. Despite the growing evidence of an association of SNXs with neurodegeneration, SNX13 deficiency has not been associated with GDD or ID. In this study, we present the case of a 4-year-old boy with brain dysplasia and GDD, including language delay, cognitive delay, and dyskinesia. Exome sequencing revealed a 1-bp homozygous deletion in SNX13 (NM_015132.5: exon8: c.742_743del; p.Tyr248Leufs*20), which caused a frameshift and predicted early termination. Sanger sequencing confirmed that the variant was inherited from his parents respectively. Our findings associate SNX13 variation with GDD for the first time and provide a new GDD candidate gene.

@article{tao2021-34879376,
  author  = {Tao, X. and Che, Y. and Li, C. and Ruan, W. and Xu, J. and Yu, Y. and Yang, F. and Wang, J. and others},
  title   = {{Novel SNX13 Frameshift Variant in an Individual with Developmental Delay}},
  journal = {Cytogenetic and genome research},
  year    = {2021},
  doi     = {10.1159/000520296},
  pmid    = {34879376},
  url     = {https://doi.org/10.1159/000520296}
}

Key findings

• Recently, an increasing number of genes have been associated with global developmental delay (GDD) and intellectual disability (ID).
• SNXs have been reported to be associated with several disorders, including Alzheimer disease and Down syndrome.
• Despite the growing evidence of an association of SNXs with neurodegeneration, SNX13 deficiency has not been associated with GDD or ID.
• Exome sequencing revealed a 1-bp homozygous deletion in SNX13 (NM_015132.5: exon8: c.742_743del; p.Tyr248Leufs*20), which caused a frameshift and predicted early termination.
• Our findings associate SNX13 variation with GDD for the first time and provide a new GDD candidate gene.

Why it matters

This single case report links a newly found SNX13 gene change to developmental delay in one child, not to Alzheimer's disease. It provides no evidence about treating, curing or preventing Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1159/000520296
• PubMed: 34879376
• Original source →
• Free full text: Cytogenetic and Genome Research →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Related studies in Down syndrome and Alzheimer's

• The importance of understanding individual differences in Down syndrome F1000Research · 2016-03-23 · usefulness score 40/100
• High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC Journal of neuroscience methods · 2004-10-01 · usefulness score 31/100
• Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients Science (New York, N.Y.) · 1998-01-01 · usefulness score 41/100
• Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies Neurology · 2006-01-01 · usefulness score 39/100
• Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1996-11-01 · usefulness score 49/100
• Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome Brain & development · 2003-04-01 · usefulness score 36/100

Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• [Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome] La Clinica terapeutica · 1994-02-01 · usefulness score 30/100 · Down syndrome and Alzheimer's
• Cerebrovascular pathology in Down syndrome and Alzheimer disease Acta neuropathologica communications · 2017-12-01 · usefulness score 51/100 · Down syndrome and Alzheimer's
• Dementia in Down's syndrome The Lancet. Neurology · 2016-04-11 · usefulness score 51/100 · Brain tissue and pathology

Similar studies

• Motion perception deficit in Down Syndrome 2015 · Down syndrome and Alzheimer's
• Molecular misreading of genes in Down syndrome as a model for the Alzheimer type of neurodegeneration 1999 · Down syndrome and Alzheimer's
• Differential susceptibility to neurofibrillary pathology among patients with Down syndrome 1996 · Down syndrome and Alzheimer's
• New approaches to studying early brain development in Down syndrome 2019 · Digital health tools
• Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis 2013 · Down syndrome and Alzheimer's
• Functional genomics of the Down syndrome 2001 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Isoprostanes - A novel major group of oxidative stress markers International journal of occupational medicine and environmental health · 2016-01-01 · usefulness score 33/100
• Newest in this subject Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

See all studies in Down syndrome and Alzheimer's →