ESPE Abstracts

Background: CFAP126 gene does play a role in the regulation of pancreatic beta cell. Literature suggests that CFAP126 was significantly downregulated in human islet cells of pre-diabetic as compared to non-diabetic and further downregulated in type 2 diabetics. However, to date CFAP126 has not been reported to cause clinical diabetes. We are reporting 2 diabetic siblings, with strong family history of type 2 diabetes on maternal side, carrying a novel heterozygous variant of CFAP126 gene.

Case summary: Two siblings (both females) from non-consanguineous parents presented with incidental hyperglycaemia at the age of 16 years (sibling 1) and 13 years (sibling 2). There was a strong history of type 2 diabetes on maternal side including mother, 2 maternal uncle, 4 maternal aunt, and maternal grandmother. Siblings 1 and 2 had BMI of 16 kg/m2 and 23.07 kg/m2 respectively without any clinical evidence of insulin resistance. Investigation revealed that sibling 1 had HbA1C of 12.3%, insulin (6.6 IU/L) and C peptide 1.8 ng/ml. Sibling 2 had HbA1C of 12.6%, insulin level (7.3 IU/L) and C peptide 2.02 ng/ml. Both were negative for anti-GAD65 and anti-insulin antibodies and had normal celiac screen and thyroid profile. They were started on basal bolus insulin with total dose of 1 unit/kg/day (sibling 1) and 0.7 unit/kg/day (sibling 2) and genetic were sent for MODY. On 3 month follow up both siblings 1 and 2 were having good control of diabetes with HbA1C of 6.6% and 6% respectively. However, their whole exome sequencing turned out to be negative for all variant of MODY gene, but a heterozygous mutation was identified in CFAP126 gene with variant c.310A>T p. (Lys104*) in both siblings and mother. After informed consent and counselling, glibenclamide was started in both sibling with written plan of gradual tapering of insulin if needed. Sibling 2 is on glibenclamide for last 3 months with obvious reduction of insulin requirement from 0.7 unit/kg/day to 0.2 unit/kg/day, recent HBA1C of 6.6%, and C peptide of 4.82 ng/ml. Sibling 1 was on glibenclamide for last one month with reduction of insulin requirement from 1 unit/kg/day to 0.5 unit/kg/day.

Conclusion: Mutation in CFAP126 seems to be associated to cause diabetes which do respond to oral sulfonylurea. Further studies are needed to confirm the effect of this gene on insulin secretion at molecular level.