Diabetes and CFAP126 gene mutation; are they really linked together?

OBJECTIVES: We are reporting a rare case series of 2 siblings and their mother with diabetes having a CFAP126 gene mutation. CASE PRESENTATION: Two female siblings, presented with incidental hyperglycemia at the ages of 16 and 13. They had a strong family history of diabetes on the maternal side. The systemic examination was unremarkable. Sibling 1 had HbA1C of 12.3 % with insulin and C-peptide levels of 6.6 IU/L and 1.8 ng/mL, respectively. Sibling 2 had an HbA1C of 12.6 %, an insulin level of 7.3 IU/L, and a C-peptide level of 2.02 ng/mL. Anti-GAD-65 and IA2 antibodies were negative. Mother also shared similar clinical processes and exhibited comparable biochemical changes related to glucose metabolism with elevated HbA1C levels and negative autoimmune markers (anti-GAD65 and IA2 antibodies). Whole exome sequencing (WES) turned out to be negative for MODY variants but revealed a rare heterozygous mutation in the CFAP126 gene (c.310A>T p. (Lys104*) in this family including both siblings and mother. The pathogenicity prediction tool MutationTaster® classified the mutation as disease causing. Oral glibenclamide remarkably reduced insulin requirements and improved HbA1C levels. CONCLUSIONS: This rare genetic mutation is likely associated with diabetes and possibly a novel marker for a yet to be identified type of diabetes, that is responsive to oral sulfonylureas. The influence of this gene on insulin secretion needs to be confirmed through future research.

Corticosterone Methyl Oxidase Type 1 (CMO1) Deficiency Due to CYP11B2 Mutation: Two Case Reports.

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive condition due to an inactivating mutation in CYP11B2. There are two types of ASD depending upon level of defect in aldosterone synthesis, corticosterone methyl oxidase type 1 (CMO 1) and type 2 (CMO 2) deficiency. We are reporting two cases of CMO 1 deficiency presented with failure to thrive. Both cases were born to consanguineous parents and presented at around 17 months and 15 months with complaints of repeated vomiting and failure to thrive. They were found to have persistent hyponatremia, hyperkalemia, low aldosterone level, raised renin levels, normal cortisol and normal 17 hydroxyprogesterone level, suggesting the diagnosis of isolated aldosterone deficiency. Whole exome sequencing revealed that Case 1 is carrying a novel homozygous mutation in CYP11B2, c.1391_1393dup p.(Leu464dup) and Case 2 has a homozygous pathogenic variant in CYP11B2, c.922T>C p.(Ser308Pro), confirming the diagnosis of CMO 1 deficiency in both cases. After initial stabilization, both cases were started on oral fludrocortisone. They responded well and showed a good catch-up in growth and development. Aldosterone synthase deficiency is a rare condition, but it shall be suspected in infants presented with failure to thrive, hyponatremia and hyperkalemia without pigmentation and virilization.