A Suspected Mosaic 3q29 Deletion in a Patient With Autism Spectrum Disorder and Multiple Micronutrient Deficiencies: A Case Report
Shuichi YatsugaBackground
3q29 deletion syndrome (MIM #609425) is a rare genomic disorder characterized by variable expressivity and incomplete penetrance. Somatic mosaicism for a 3q29 deletion in an affected proband has rarely been documented. Mosaicism inferred from attenuation of the array signal requires confirmation by an independent method. When a chromosomal deletion encompasses an autosomal recessive (AR) disease gene, evaluation of the second allele may be informative. Extreme food selectivity associated with autism spectrum disorder (ASD) poses substantial but underrecognized nutritional risk.
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.
Conclusion
An attenuated CMA signal at 3q29, compatible with a suspected mosaic deletion but not independently confirmed, was identified in a patient whose phenotype overlaps 3q29 deletion syndrome. Where a deletion encompasses an AR disease gene whose phenotype overlaps the presentation, second‐allele evaluation may add diagnostic resolution. This case highlights the importance of considering nutritional assessment in children with ASD and extreme food selectivity; the biochemical abnormalities persisted at follow‐up, although no vitamin D had been administered before the follow‐up sample and treatment exposure and adherence were not systematically documented.