Table 1

Confirmed diagnosis genetic obesity: autosomal recessive inherited conditions (homozygous or compound heterozygous)

GeneGenotypeMCA/IDClinical information
fitting with the clinical phenotype
Additional information/coincidental phenotypic findingsBMI
Family history of obesity
(if available)
18F1 BBS7 Compound heterozygous: c.1037G>A(;)1657C>T; p.(Arg346Gln)(;)(Gln553*)YesPostaxial polydactyly fingers and toes
Intellectual deficit
onset obesity: 3 years
38.5+6.1 SD
23F2 LEPR Compound heterozygous: c.1985T>C(;)2168C>T;
onset obesity: 2 months
AD: 34 weeks, birth weight of 2605 g (+1.9 SD for age)34.5+7.5 SDNo family history of obesity
31F2 LEPR Compound heterozygous: c.2051A>C(;)2627C>A; p.(His684Pro)(;)(Pro876Gln)YesOnset obesity: 3 months
Birth weight: 3270 g (−0.4 SD for gestational age)
Cleidocranial dysplasia (RUNX2 mutation identified)34.6+7.3 SDNo family history of obesity
417M2 MC4R Compound heterozygous: c.446_450del(;)644T>G; p.(Phe149fs)(;)(Met215Arg)NoOnset obesity: 1 yearHypogonadism43.8No family history of obesity
518M2 MC4R Homozygous: c.779C>A(;) 779C>A; p.(Pro260Gln)(;)(Pro260Gln)NoOnset obesity: 1 yearAutism40.3No childhood obesity in the parents, current BMI of father 32.9 kg/m2
615M2 SPG11 Compound heterozygous: c.4534dup(;)5857?_
6477+?del; p.(Asp1512fs)(;)
YesSpastic paraparesis
IQ: 48
Onset obesity: 3 years
37.9+3.7 SDMother and brother obese
  • Medical centre: 1=UMC Utrecht Clinical Genetics; 2=CGG Pediatrics.

  • *A singleasterisk is here used as a symbol for translation termination (stop) codon.

  • †The intragenic deletion in SPG11, comprising multiple protein coding exons, was identified after additional Sanger sequencing and MLPA copy number analysis at the DNA diagnostics department of the Radboud UMC, Nijmegen, The Netherlands. The NGS platform used at the time the patients in the present study were analysed is not suitable for reliable detection of genomic deletions>6 bp.