A small 7p22.3 microdeletion: Case report of SNX8 haploinsufficiency and neurological findings

Chromosome 7

A small 7p22.3 microdeletion: Case report of SNX8 haploinsufficiency and neurological findings

7p22.3 microdeletion, a small deletion within the short arm of chromosome 7, has been reported in the literature before, but the genotype-phenotype correlation remains uncertain. Clinical features in previous cases include developmental delay, intellectual disability, congenital heart disease, and dysmorphic features.

The authors report on a four-year-old boy with a 139 Kb deletion at 7p22.3, inherited from a mosaic mother. This deletion involved MAD1L1, FTSJ2, NUDT1 and SNX8 genes. The boy was diagnosed with left kidney agenesis, attention deficit hyperactivity disorder, and a generalized developmental delay. Additionally, he presented significant difficulties in the socio-emotional, motor, and cognitive domains. However, no cardiac defects were found.

SNX8 is expressed in hippocampal and cerebellar neurons, and together with previous observations the authors suggest that this gene plays a role in neurodevelopment. Moreover, SNX8 has been identified in the literature as a likely candidate gene for the cardiac defects seen in some patients with 7p22.3 deletion. The authors speculate that SNX8 haploinsufficiency may be necessary but not sufficient for the cardiac malformations as they were absent in the patient. Conversely, the EIF3B gene deleted in other patients but not in the current patient may be involved in heart development.

According to the literature mutations affecting the EIF3B ortholog in zebrafish has been implicated in congenital heart defects. This makes the EIF3B gene a likely candidate gene for heart development and should be studied further.

The article concludes that SNX8 is the most likely gene responsible for the neurodevelopmental problems found in the current patient.

Mastromoro G. et al. “Small 7p22.3 Microdeletion: Case Report of Snx8 Haploinsufficiency and Neurological Findings.” European Journal of Medical Genetics, 2019, [ahead of print], doi:10.1016/j.ejmg.2019.103772.

Articles of the month are chosen from newly published genetic research by CDO consulting medical advisor and geneticist, Dr. Iosif Lurie, M.D. PhD  For more information on any article please contact info@chromodisorder.org