Figure 1.

Partial pedigrees. Pedigrees of the four families demonstrate co-segregation of the p.R76W HNF4A mutation with neonatal hypoglycaemia and Fanconi syndrome. The genotype is given below each symbol where known. For each proband, age at follow-up, mutation, birth weight Z score, hypoglycaemia treatment and duration, age of diabetes diagnosis/diabetes management, age of diagnosis of Fanconi syndrome, glomerular filtration rate (GFR) (mLs/min/1.73 m²) and height Z score are provided. The mutation is reported according to the HNF4A cDNA sequence published by Chartier et al¹⁷ but has also been described as p.R85W according to reference sequence NM_000457.3 or p.R63W using NM_175914.3 (LRG_483).²² Birth weight and height Z scores are calculated from UK 1990 child growth including standard children and preterm infants. Our proband's grandfather developed diabetes at 51 years of age with a body mass index (BMI) of 30.5. He is managed with weight loss alone with a recent HbA1c of 39 mmol/mol. The mutation was present in his leukocyte DNA at 26% but it is not known if the mutation load in his pancreas is sufficient to cause his diabetes. He had no reported neonatal hypoglycaemia or Fanconi syndrome (data not shown). Neither the proband, his mother, nor her sister are currently diabetic, but they undergo surveillance using an annual oral glucose tolerance test.