Background: METTL5 is a conserved RNA methyltransferase responsible for catalyzing the N6-methyladenosine (m6A) modification of 18S ribosomal RNA, a process critical for ribosome biogenesis and translational regulation. Biallelic variants in METTL5 have been linked to autosomal recessive intellectual developmental disorder-72 (MRT72), typically presenting with microcephaly, intellectual disability, and speech delay.However, the association between METTL5 and isolated attention-deficit/hyperactivity disorder (ADHD) remains underexplored.Case Presentation: We report a novel homozygous missense variant in METTL5 (c.617G>A; p. Arg206Gln) identified via trio-based whole-genome sequencing in a 14-year-old Qatari female with ADHD, microcephaly, speech delay, and mild intellectual disability. Both consanguineous parents are heterozygous carriers and clinically unaffected, consistent with autosomal recessive inheritance. In silico tools predict the variant to be deleterious, and the affected residue is evolutionarily conserved.Conclusion: This is the first report to associate a homozygous METTL5 p. Arg206Gln variant with a formally diagnosed ADHD phenotype, thereby expanding the clinical spectrum of METTL5-related neurodevelopmental disorders.The findings highlight the importance of genomic testing in complex behavioral presentations and support the inclusion of METTL5 in gene panels for neurodevelopmental conditions.
