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Obesity and developmental delay in a patient with uniparental disomy of chromosome 2

International Journal of Obesity volume 40, pages 1935–1941 (2016)Cite this article

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Abstract

Objective:

Uniparental disomy (UPD) is an unusual situation wherein two homologous chromosomes are inherited from the same parent. UPDs can cause clinical abnormalities owing to the aberrant dosage of genes regulated by epigenetic imprinting or homozygosity of variants for recessive phenotypes. The aim of this study was to identify the genetic cause of the obesity and developmental delay phenotype in a 3-year-old Chinese boy.

Study Design:

Chromosomal microarray analysis (CMA) was used for detecting potential copy number variations (CNVs) and homozygous segments. Whole-exome sequencing (WES) identified sequence variants. Sanger sequencing further confirmed the variants in GPBAR1 and CAPN10 both in the patient and the parents.

Results:

No clinically significant CNVs were identified by CMA but a complete UPD of chromosome 2 (UPD2) was revealed in the patient. WES identified a total of 13 rare homozygous single-nucleotide variants (SNVs) on chromosome 2. Among the 13 SNVs, a nonsense variation in GPBAR1 (c.753T>G; p.Y251*) and a missense variation in CAPN10 (c.413C>T; p.S138F) were evaluated as candidate disease-causing variants based on their functional impacts to their respective protein and the biological relevance of the genes to the clinical presentation of our patient. Both GPBAR1 and CAPN10 variants were detected in the patient’s mother in a heterozygous state, indicating that the patient had maternal UPD2. No other clinically relevant variants were identified.

Conclusions:

Homozygosity of rare recessive variations caused by UPD2 likely contributed to the phenotypes of our patient. Based on emerging evidence, the nonsense variation in GPBAR1 and the missense variation in CAPN10 are considered as causally related to our patient’s phenotype, that is, obesity and delayed development, respectively. The present study further supports the role of GPBAR1 in obesity and the role of calpain-10 in neurological function.

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Acknowledgements

We thank all the members of the family for their participation in this study. This research was supported by the National Natural Science Foundation of China (Grant Nos. 81472051 and 81371903), Project of Shanghai Municipal Science and Technology Commission (Grant No. 15410722800) and Project of Shanghai Municipal Education Commission- Gaofeng Clinical Medicine (Grant No. 20152529).

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Author notes

  1. T Yu and J Li: These authors contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Medical Genetics, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China

    T Yu, N Li, Y Shen, X Wang & J Wang

  2. Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China

    T Yu, N Li & J Wang

  3. Department of Internal Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China

    J Li, Y Ding, G Chang, Y Chen & X Wang

  4. Department of Neurology, Gui Zhou Provincial People’s Hospital, Guizhou, China

    R Liu

  5. Department of Laboratory Medicine, Boston Children’s Hospital, Boston, USA

    Y Shen

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Correspondence to X Wang or J Wang.

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Yu, T., Li, J., Li, N. et al. Obesity and developmental delay in a patient with uniparental disomy of chromosome 2. Int J Obes 40, 1935–1941 (2016). https://doi.org/10.1038/ijo.2016.160

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