Case presentation
An 8-year-old Japanese boy with ASD, intellectual disability, absent speech, progressive obesity, hepatosplenomegaly, and congenital toe syndactyly underwent chromosomal microarray analysis (CMA). A 1.27-Mb interval at 3q29 (arr[GRCh37] chr3:195,804,728-197,074,949) was segmented with a mean log2 ratio of -0.252 across 59 informative probes, against an excellent array quality (derivative log ratio spread 0.179). The signal returned to baseline immediately outside the interval. The magnitude of the attenuation is intermediate between a normal diploid state and that expected for a constitutional heterozygous deletion and is compatible with a suspected mosaic deletion; the laboratory's automated nomenclature nevertheless assigned a copy number of 2, with the explicit caveat that copy number was not verified, and no independent confirmatory method was applied. The interval is atypical and nested within the recurrent 3q29 region and encompasses TFRC, RNF168, PAK2, and DLG1. A targeted 15-gene DNA repair panel identified no pathogenic or likely pathogenic variant on the second RNF168 allele. An incidental heterozygous NBN variant of uncertain significance (c.265A > G, p.Ile89Val; NM_002485.5) was nondiagnostic and did not alter management. Neither exome nor genome sequencing was available as a reimbursed clinical investigation, and parental samples were not obtained. Microcytosis and hypochromia were present at both time points; serum iron was within the reference interval at baseline and low at follow-up, ferritin remained within the reference interval throughout, and no threshold-based criterion for iron deficiency was met. Low 25-hydroxyvitamin D, low vitamin C, and low retinol-binding protein were documented at two time points and considered most likely related to the markedly restricted diet. Plasma amino acids; serum carnitine fractions; zinc; selenium; vitamins B1, B2, and B12; immunoglobulins; and alpha-fetoprotein were unremarkable; serum copper was elevated in the presence of a raised C-reactive protein, and ceruloplasmin was not measured. The cause of the hepatosplenomegaly remained unresolved.
