A missense variant, p.(Ile269Asn), in MC4R as a secondary finding in a child with BCL11A-related intellectual disability

Daniah T Beleford; Jessica Van Ziffle; Ugur Hodoglugil; Anne M Slavotinek

doi:10.1016/j.ejmg.2020.103969

A missense variant, p.(Ile269Asn), in MC4R as a secondary finding in a child with BCL11A-related intellectual disability

Eur J Med Genet. 2020 Sep;63(9):103969. doi: 10.1016/j.ejmg.2020.103969. Epub 2020 Jun 10.

Authors

Daniah T Beleford¹, Jessica Van Ziffle², Ugur Hodoglugil³, Anne M Slavotinek⁴

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: daniah.beleford@ucsf.edu.
² Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
³ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
⁴ Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: anne.slavotinek@ucsf.edu.

PMID: 32534219
DOI: 10.1016/j.ejmg.2020.103969

Abstract

We describe a three year old female who underwent clinical exome sequencing and was diagnosed with BCL11A-related intellectual disability/Dias-Logan syndrome due to a de novo, heterozygous variant in the BCL11A gene, NM_018014.3:c.148C > T; p.(Gln50*). A missense variant in MC4R, NM_005912.3:c.806T > A; p.(Ile269Asn), was also reported as a secondary finding. In her family, her father, paternal aunt, and paternal uncle were all reported to have height and weight measurements suggestive of Class 3 obesity with BMI>40 kg/m². The MC4R gene is not currently listed among those recommended for reporting of secondary findings by the American College of Medical Genetics and Genomics (ACMG). The identification of genetic risk factors for obesity is an emerging field without established guidelines for the care of patients who are found to have a predisposing genetic variant for obesity as a secondary finding. Management suggestions include interventions for weight-management, early screening for obesity-related co-morbidities, such as diabetes and dyslipidemia, and targeted therapies, such as MC4R agonists.

Keywords: BCL11A; Developmental delay; Dias-Logan syndrome; Intellectual disability; MC4R; Obesity; Secondary findings.

Publication types

Case Reports
Letter

MeSH terms

Child, Preschool
Developmental Disabilities / genetics*
Developmental Disabilities / pathology
Female
Humans
Intellectual Disability / genetics*
Intellectual Disability / pathology
Mutation, Missense*
Receptor, Melanocortin, Type 4 / genetics*
Repressor Proteins / genetics*

Substances

BCL11A protein, human
MC4R protein, human
Receptor, Melanocortin, Type 4
Repressor Proteins