WDR4 and Isolated Growth Hormone Deficiency Type IA

A recent report has implicated WDR4 in isolated growth hormone deficiency type IA based on a single 6‑year‑old patient manifesting motor delay, growth delay, delayed speech and language development, and intellectual disability. In this case, whole exome sequencing revealed compound heterozygous variants in WDR4, including the missense change c.491A>C (p.Asp164Ala) and an additional frameshift mutation. These variants segregated with the condition in an autosomal recessive inheritance pattern, providing genetic evidence that deleterious alterations in WDR4 can impair normal growth and neurodevelopment (PMID:29597095).

Biological studies further support a role for WDR4 in human development by demonstrating its essential function in tRNA methylation and cell cycle regulation. Although most functional assessments have been performed in contexts other than isolated growth hormone deficiency type IA, these experiments reveal a mechanistically plausible pathway by which WDR4 loss‐of‐function may contribute to growth and neurodevelopmental disturbances (PMID:29983320). Key take‑home sentence: Incorporating WDR4 evaluation into the diagnostic workup of patients with growth and developmental delays may facilitate early, targeted patient management.

References

• European journal of medical genetics • 2018 • Speech and language delay in a patient with WDR4 mutations PMID:29597095
• Molecular cell • 2018 • Mettl1/Wdr4-Mediated m7G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation PMID:29983320

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