KRBOX4 and Intellectual Disability

KRBOX4 (HGNC:26007) has been implicated in intellectual disability (MONDO_0001071) based on limited clinical observations. A case report documented a patient with intellectual disability and global developmental delay in whom a genomic duplication encompassing KRBOX4 along with other zinc finger transcription factors was identified (PMID:20691945). This finding raises the possibility that alterations involving KRBOX4 may contribute to neurodevelopmental deficits. In a separate multi‐patient study focused on contiguous gene syndromes, KRBOX4 was included among several candidate genes in patients with intellectual disability and features of X‑linked mental retardation (PMID:16385466). However, these studies relied on array‑based comparative genomic hybridization and did not isolate a specific coding variant in KRBOX4.

Genetic evidence remains limited because no distinct pathogenic coding change has been reported for KRBOX4; the available data are based solely on copy number variations that co‐occurred with alterations in neighboring genes. Segregation details were not provided, and dedicated functional assays addressing the role of KRBOX4 in cognitive development are lacking. While the duplication events observed in affected individuals tentatively support a role for KRBOX4 in intellectual disability, alternative candidate genes within the rearranged genomic region may also be contributory. Key take‑home: Additional targeted studies are required to clarify KRBOX4’s contribution to intellectual disability and to establish its clinical utility.

References

• Pediatric neurology • 2010 • Developmental disability: duplication of zinc finger transcription factors 673 and 674. PMID:20691945
• American journal of human genetics • 2006 • ZNF674: a new kruppel-associated box-containing zinc‑finger gene involved in nonsyndromic X‑linked mental retardation. PMID:16385466

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