Table 1.
Clinical and molecular characteristics of MODY probands and their family members with diabetes.
| Patient ID | Sex/Current age, years | Age at diagnosis, years | BMIa, kg/m2 | Fasting plasma glucosea, mmol/L | HbA1c values (at diagnosis–last follow up), % | Diabeticketosis/ketoacidosisa | TreatmentFollow-up | Complications | Probability of MODY, % | Gene(RefSeq) | Variants | Genotype | dbSNP ID | MAF in GnomAD | Pathogenicity according to ACMG b, SIFTc, Polyphen-2d Proveane, HSFf | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F1-IV.2† | M/8.3 | 4.3 | 15.1 | 6.81 | 6.2–6.5 | No | OHA for two years then shifted to diet. | No | 75.5 | GCK NM_000162.5 | Exon 5: c.571C>T, p.Arg191Trp | CT | rs1085307455 | 7.96e−06 | Pathogenic c,d | ClinVar, VarSome, LitVar‡ |
| F2-III.11 | F/63 | 40 | n.a. | n.a. | n.a.–9 | No | Metformin | No | n.a. | GCK NM_000162.5 | Exon 7: c.774C>T, p.(Gly258Gly) | CT | rs780806456 | 1.77e−05 | Uncertain significance b, affect splicing f | Present study |
| KLF11 NM_003597.5 | Exon 2 : c.185A>G, p.Gln62Arg | AG | rs35927125 | 9.13e−02 | Benign c,d | ClinVar, VarSome, LitVar‡ | ||||||||||
| F2-IV.12† | M/33.3 | 27 | 17.35 | 29.5 | 13.2–12.2 | ketoacidosis | Initial treatment on insulin (0.2 IU/kg/day). Shifted to OHA after two years. Current treatment with insulin at a dose of 0.3 IU/kg/day |
No | 24.4 | GCK NM_000162.5 | Exon 7: c.774C>T, p.(Gly258Gly) | TT | rs780806456 | 1.77e−05 | Uncertain significance b, affect splicing f | Present study |
| KLF11 NM_003597.5 | Exon 2 : c.185A>G, p.Gln62Arg | AG | rs35927125 | 9.13e−02 | Benign c,d | ClinVar, VarSome, LitVar‡ | ||||||||||
| F2-IV.16 | F/40 | 33 | n.a. | n.a. | n.a.– 8 | No | Metformin | No | n.a. | GCK NM_000162.5 | Exon 7: c.774C>T, p.(Gly258Gly) | TT | rs780806456 | 1.77e−05 | Uncertain significance b, affect splicing f | Present study |
| KLF11 NM_003597.5 | Exon 2 : c.185A>G, p.Gln62Arg | GG | rs35927125 | 9.13e−02 | Benign c,d | ClinVar, VarSome, LitVar‡ | ||||||||||
| F3-II.10 | M/61 | 40 | n.a. | n.a. | n.a.–8.5 | No | Metformin and glimepiride | No | n.a. | HNF1A NM_000545.8 | Exon 1 : c.293C>T, p.Ala98Val | CT | rs1800574 | 2.82e−02 | Benign c,d | ClinVar, VarSome, LitVar‡ |
| F3-III.1† | M/30 | 22 | 25.59 | 8.5 | 8–9 | No | Metformin and glimepiride | No | 75.5 | |||||||
| F4-III.2 | F/65 | 38 | n.a. | n.a. | n.a.–9 | No | Metformin | No | n.a. | ABCC8 NM_001287174.2 | Exon 25 : c.2978G>A, p.(Arg993His) | GA | rs201499958 | 3.59e−05 | Tolerated c, probably damaging d, damaging e | Present study |
| F4-IV.2 | F/37 | 24 | 19 | 19.5 | 8.5–11 | No | Diet for 3 years, then metformin for 2 years—before starting insulin (0.7 IU/kg/day) + metformin | Diabetic nephropathy and retinopathy | 75.5 | GG | ||||||
| F4-IV.8† | M/33 | 19 | 19.5 | 23 | 10–13 | Ketosis | Insulin (0.7 IU/kg/day) and metformin were started three years after the first diagnosis. | 58 | AA |
BMI, Body Mass Index; HbA1c, glycated hemoglobin; n.a., Not available; OHA, oral hypoglycemic agents. aBMI and fasting plasma glucose values at first admission with/without the acute metabolic disorder. The probability of MODY was calculated only for the young-onset diabetes patients using MODY probability calculator. b,c,d,e,fThe prediction of the deleterious effect of variants using different tools. The estimated minor allele frequency for HNF1A p.A98V variant was around 3%; while the GCK p.(Gly258Gly) variant was absent in 50 healthy subjects. The restriction enzymes HaeIII and HinP1I were used to digest the PCR products covering the rs1800574 and rs780806456, respectively. †Index case. ‡Variant found in LitVar (23).