A. Cayir, A. Turkyilmaz, H. Rabenstein, F. Guven, YS. Karagoz, D. Vuralli, M. Wabitsch, et al. (2024). Severe Early-Onset Obesity and Diabetic Ketoacidosis due to a Novel Homozygous c.169C>T p.Arg57* Variant in CEP19 Gene. Molecular syndromology, 15(2), 104-113. https://doi.org/10.1159/000535253

PubMed 38585545

[Abstract]
INTRODUCTION: Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The "centrosomal protein 19 (CEP19)" gene encodes for a centrosomal and ciliary protein. Homozygous variants in the CEP19 gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features.

METHODS: Sanger sequencing and whole-exome sequencing were performed to identify the genetic etiology in the family.

RESULTS: The index case was a 12-year-old female who presented with severe obesity (BMI of 62.7 kg/m2), metabolic syndrome, and diabetic ketoacidosis. Her nonidentical twin female siblings also had early-onset severe obesity, metabolic syndrome, and diabetes. In addition, one of the affected siblings had situs inversus abdominalis, polysplenia, lumbar vertebral fusion, and abnormal lateralization. A novel homozygous nonsense (c.169C>T, p. Arg57*) pathogenic variant was detected in exon 3 of the CEP19 gene in all affected members of the family. One unaffected sister and unaffected parents were heterozygous for the variant. This variant is predicted to cause a stop codon at amino acid sequence 57, leading to a truncated CEP19 protein.

DISCUSSION/CONCLUSION: Our study expands the phenotypical manifestations and variation database of CEP19 variants. The findings in one of our patients reaffirm its role in the assembly and function of both motile and immotile cilia.