Complex genetic interactions in a Jordanian pediatric patient with a rare oligogenic disorder: A case report

We present a case of a 6-year-old Jordanian male patient with intrauterine growth retardation, fine and gross motor delay, recurrent infections, respiratory and gastrointestinal problems, immunodeficiency, and distinctive dermatological abnormalities. Comprehensive genetic evaluation identified a homozygous pathogenic variant in the cystatin A gene (c.64A>T; p. Lys22Ter), consistent with a diagnosis of acral peeling skin syndrome. Furthermore, two variants of uncertain significance were identified in BACH2 (c.100G>A; p. Asp34Asn, heterozygous) and NSMCE3 (c.877G>A; p. Ala293Thr, homozygous). These two genes may contribute to the patient?s immunodeficiency and genomic stability. The patient was also a heterozygous carrier of pathogenic variants in the MEFV gene (c.2230G>T; p. Ala744Ser) linked to familial Mediterranean fever. Carrier status was also noted for the phenylalanine hydroxylase gene (c.157C>T; p. Arg53Cys). This gene is linked to phenylketonuria. To the best of our knowledge, this is the first case study that was confirmed by clinical, biochemical, and molecular genetic findings in Jordan. This case underscores the utility of comprehensive genomic analysis in accurately diagnosing complex genetic disorders and highlights the necessity of phenotypic correlation in variant interpretation and future patient management.