GPR126 – Autosomal Recessive Intellectual Disability

GPR126 (ADGRG6) has been implicated in autosomal recessive intellectual disability (ID) based on whole exome sequencing in a consanguineous family. A homozygous missense variant, c.3264G>C (p.Trp1088Cys), was identified in two affected siblings presenting with profound ID, severe speech impairment, microcephaly, infantile seizures, spasticity, and cerebellar hypoplasia ([PMID:30549416]). No additional families or segregation beyond the index cases have been reported.

GPR126 encodes an adhesion G protein–coupled receptor critical for radial sorting and myelination in Schwann cells, suggesting a loss‐of‐function mechanism underlying neurological impairment in ID ([PMID:30549416]). Although the study provides a plausible pathomechanism, evidence is limited to a single variant in one family, and functional assays specific to ID are lacking. Key take-home: include GPR126 in gene panels for autosomal recessive ID but pursue further genetic replication and functional validation.

References

• American journal of medical genetics. Part A • 2019 • GPR126: A novel candidate gene implicated in autosomal recessive intellectual disability. PMID:30549416

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