eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-03-20 19 1 503 510 10.13005/bpj/3369 70955 article Yousef Al-Hajaya 1 Department of Biological Sciences, Faculty of Science, Mutah University, Karak, Jordan Multiple congenital anomalies-hypotonia-seizures syndrome type 4 (MCAHS4, OMIM: 618548) is a rare autosomal recessive neurological disorder caused by biallelic causal variants in PIGQ gene (OMIM 605754). Whole genome sequencing was performed in a 4-year-old male presenting with clinical features consistent with MCAHS4. A homozygous frameshift variant in PIGQ gene (c.1673del; p. Gly558fs*25) was identified and subsequently confirmed through parental segregation analysis. This variant is located in the final exon and is not predicted to efficiently undergo nonsense-mediated mRNA decay, potentially resulting in the production of a truncated protein with impaired enzymatic function. However, it remains classified as a variant of uncertain significance according to ACMG/AMP guidelines due to the absence of functional validation. Additional carrier status and pharmacogenomic findings were identified but are not directly related to the proband’s presenting clinical phenotype. Collectively, these results provide additional interpretative evidence consistent with PIGQ-related disorder and underscores the importance of integrative genome-wide analysis and cautions variant interpretation in rare neurodevelopmental disorders. https://biomedpharmajournal.org/vol19no1/integrative-genomic-and-genotype-phenotype-analysis-of-a-homozygous-pigq-frameshift-variant-in-mcahs4/ Carrier Status Developmental Delay Frameshift Variants Pharmacogenomics Association PIGQ Whole Genome Sequencing