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. 2024 Dec 5;17(1):31.
doi: 10.1186/s13039-024-00700-5.

Clinical and genomic profiling of a patient with a de novo ring chromosome 18: a case report highlighting autoimmune and neurological implications

Annalaura Montanari #  1 , Paola Caforio #  2 , Annalisa Paparella  1 , Paola Casieri  2 , Maria Cristina Nuzzi  2 , Maria Fatima Antonucci  2 , Claudia Rita Catacchio  1 , Marilina Tampoia  2 , Mattia Gentile  3 , Roberta Bucci  3 , Valerio Cecinati  2 , Angelo Cellamare  4 , Francesca Antonacci  5
Affiliations

Clinical and genomic profiling of a patient with a de novo ring chromosome 18: a case report highlighting autoimmune and neurological implications

Annalaura Montanari et al. Mol Cytogenet. .

Abstract

Ring chromosome 18 (r(18)) is a rare chromosomal abnormality characterized by the circular rearrangement of chromosome 18, which presents significant challenges in genotype-phenotype correlations due to variability in deletions across the 18p and 18q arms. We report the case of a pediatric patient with a de novo ring chromosome 18, diagnosed by karyotype analysis and confirmed by high-resolution SNP arrays. The patient exhibited pathogenic copy number variants (CNVs) in the 18p11.32p11.22 and 18q23 regions, involving 36 and 10 OMIM genes, respectively. Clinically, the patient presented with hypothyroidism secondary to autoimmune thyroiditis, autoimmune hepatitis type II, and genetic predisposition to celiac disease and insulin-dependent diabetes mellitus (IDDM) along with notable dysmorphic features. The 18q microdeletion encompasses the MBP gene, involved in the development and functionality of the nervous system, as supported by hypotonia and gliosis shown by the MRI. This case highlights the complex interplay between genetic imbalances on chromosome 18 and autoimmune phenotypes, emphasizing the need for ongoing research to elucidate underlying mechanisms and optimize clinical management for individuals with r(18).

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Conflict of interest statement

Declarations. Ethical Approval: Written informed consent to perform genetic testing and further studies was obtained from the family. The parents also consented to publishing photos of the patient. This case report represents a detailed report of an individual patient identified during routine diagnostics and does not belong to a larger project for which ethics committee approval is required. Therefore, ethical review and approval were waived for this study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The karyotype illustrates the chromosomal makeup of our proband, showing the presence of a ring shaped chromosome 18
Fig. 2
Fig. 2
High-resolution SNP array analysis shows the presence of a deletion at 18p11.32p11.22 and a microdeletion at 18q23 in the proband. The left panel (A) showcases log R ratios (LRR) across chromosome 18, offering a normalized measure of signal intensity to evaluate CNVs. For each SNP, 0 indicates a typical, diploid copy number, while positive and negative values suggest copy number gains and losses, respectively. The right panel (B) depicts B allele frequency (BAF) values, assessing the proportion of two alleles present at a specific genomic locus. BAF values of 1, 0.5, and 0 correspond to homozygous for the reference allele (BB), heterozygous (AB), and homozygous for the alternative allele (AA) genotypes, respectively. The LogR plot displays a significant decrease in signal intensity in the regions 18p11.32p11.22 and 18q23, suggesting the presence of two deletions (copy number of x1). Likewise, the BAF plot confirms the loss of heterozygosity, affirming the existence of the two hemizygous deletions
See this image and copyright information in PMC

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