Characteristics of patients diagnosed with monogenic diabetes and details of mutations found for those recruited but diagnosed with monogenic diabetes prior to the study and those diagnosed as a result of the biomarker pathway
ID | Genetic characteristics | Clinical characteristics | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Gene | Method | Zygosity | DNA level description | Age at diagnosis (years) | Treatment | Parent with diabetes | BMI | HbA1c | Age at recruitment (years) | Additional clinical features | |
Recruited but diagnosed prior to the UNITED study | |||||||||||
211 | GCK | Sanger | Het | c.97_117dup | 3 | Diet | Yes | 34.0 | 48 | 16 | |
523 | GCK | Sanger | Het | c.97_117dup | 27 | Diet | No | 51.7 | 55 | 43 | |
537 | GCK | Sanger | Het | c.683C>T | 11 | Diet | Yes | 13 | |||
538 | GCK | Sanger | Het | c.683C>T | 9 | Diet | Yes | 11 | |||
542 | GCK | Sanger | Het | c.184G>A | 29 | Diet | Yes | 38.9 | 48 | 39 | |
543 | GCK | Sanger | Het | c.184G>A | 4 | Diet | Yes | 4 | |||
544 | GCK | Sanger | Het | c.184G>A | 3 | Diet | Yes | 5 | |||
1155 | GCK | Sanger | Het | c.1343G>T | 25 | Diet | Yes | 19.3 | 50 | 25 | |
82095 | GCK | Sanger | Het | c.1019G>T | 9 | Diet | Yes | 21.9 | 45 | 14 | |
535 | HNF1A | Sanger | Het | c.379_381del | 24 | OHA | Yes | 25.9 | 51 | 47 | |
547 | HNF1A | Sanger | Het | c.1748G>A | 22 | Diet | Yes | 24.4 | 40 | 30 | Low renal threshold |
554 | HNF1A | Sanger | Het | c.872dup | 18 | OHA | Yes | 30 | 86 | 39 | |
566 | HNF1A | Sanger | Het | c.872dup | 17 | OHA | Yes | 29.2 | 51 | 42 | Sulphonylurea sensitivity, low renal threshold |
603 | HNF1A | Sanger | Het | c.1420C>T | 20 | OHA | Yes | 26.5 | 56 | 42 | Low renal threshold |
617 | HNF1A | Sanger | Het | c.779C>T | 25 | Diet | Yes | 25.4 | 44 | 26 | |
892 | HNF1A | Sanger | Het | c.476G>A | 14 | Insulin | Yes | 30.0 | 63 | 40 | |
1370 | HNF1A | Sanger | Het | c.872dup | 21 | Diet | Yes | 36.1 | 83 | 21 | |
1409 | HNF1A | Sanger | Het | c.872dup | 21 | OHA+Ins | Yes | 32.8 | 95 | 42 | Sulphonylurea sensitivity |
80480 | HNF1A | Sanger | Het | c.1093_1107+6del | 19 | OHA | 22.9 | 73 | 40 | ||
82261 | HNF1A | Sanger | Het | c.185del | 12 | OHA+Ins | Yes | 23.7 | 73 | 25 | Low renal threshold |
82276 | HNF1A | Sanger | Het | c.434C>T | 13 | Insulin | Yes | 23.8 | 60 | 27 | |
82301 | HNF1A | Sanger | Het | c.1340C>T | 20 | OHA | Yes | 27.4 | 91 | 37 | |
82310 | HNF1A | Sanger | Het | c.185del | 18 | OHA | Yes | 24.4 | 48 | 45 | Low renal threshold |
82374 | HNF1A | Sanger | Het | c.1093_1107+6del | 19 | OHA | Yes | 23.8 | 83 | 20 | Sulphonylurea sensitivity |
82258 | HNF4A | Sanger | Het | c.322G>A | 28 | Insulin | Yes | 20.9 | 60 | 31 | |
600 | HNF1B | Sanger | Het | c.982_986del | 20 | Insulin | No | 23.4 | 122 | 35 | Renal cysts |
82033 | HNF1B | Sanger | Het | c.466A>G | 17 | Insulin | No | 25.3 | 54 | 35 | Genital tract malformations, renal hypoplasia |
82006 | KCNJ11 | Sanger | Het | c.601C>T | 0 | OHA | No | 26.6 | 33 | 35 | Diagnosed at 12 weeks of age |
539 | LMNA | Sanger | Het | c.1930C>T | 17 | OHA+Ins | Yes | 24.2 | 114 | 49 | Lipodystrophy |
595 | LMNA | Sanger | Het | c.1444C>T | 21 | OHA+Ins | Yes | 25.1 | 62 | 34 | |
604 | 3243 | Hp | m.3243A>G | 27 | Insulin | Yes | 26.9 | 54 | 36 | ||
80541 | 3243 | Hp | m.3243A>G | 28 | Insulin | Yes | 26.4 | 83 | 48 | ||
82399 | 3243 | Hp | m.3243A>G | 29 | Insulin | Yes | 26.4 | 56 | 41 | Deafness | |
540 | NEUROD1 | Sanger | Het | c.616dup | 21 | OHA+Ins | Yes | 49.8 | 83 | 36 | Lipodystrophy and necrobiosis |
Identified as part of the biomarker pathway | |||||||||||
82372 | GCK | Sanger | Het | c.1340G>A | 18 | Diet | No | 25.5 | 46 | 19 | |
82316 | HNF4A | Sanger | Het | c.1064–5_1070del | 14 | Diet | Yes | 32.3 | 38 | 33 | |
377 | HNF4A | Sanger | Het | c.-12G>A | 11 | Insulin | Yes | 28.4 | 104 | 14 | |
80089 | HNF1A | Sanger | Het | c.1349dup | 30 | Insulin | Yes | 31.0 | 72 | 48 | |
80170 | HNF1A | Sanger | Het | c.391C>T | 21 | Insulin | No | 23.5 | 52 | 35 | Low renal threshold |
80173 | HNF1A | Sanger | Het | c.495G>C | 17 | Insulin | Yes | 24.5 | 56 | 46 | |
82003 | HNF1A | Sanger | Het | c.28A>C | 26 | Diet | Yes | 29.8 | 73 | 26 | |
82352 | HNF1A | Sanger | Het | c.814C>T | 13 | Insulin | Yes | 32.3 | 91 | 45 | |
82013 | HNF1A | tNGS | Het | c.-258A>G | 24 | OHA | Yes | 39.6 | 75 | 43 | |
307 | HNF1B | tNGS | Het | c.1-?_1674+?del | 29 | Insulin | No | 22.7 | 62 | 31 | Asperger syndrome, renal cysts, low fecal elastase, low magnesium |
82014 | NEUROD1 | tNGS | Het | c.616dup | 21 | OHA | No | 35.3 | 88 | 31 | |
183 | NEUROD1 | tNGS | Het | c.616dup | 29 | Insulin | No | 27.1 | 55 | 46 | |
82010 | 3243 | tNGS | Hp | m.3243A>G | 27 | OHA+Ins | Yes | 28.6 | 91 | 46 | |
82038 | PPARG | tNGS | Het | c.1154G>A | 22 | OHA | No | 26.6 | 53 | 36 | Lipodystrophy, acanthosis |
80925 | TRMT10A | tNGS | Hom | c.79G>T | 23 | OHA+Ins | No | 33.0 | 69 | 28 | Microcephaly, learning difficulties, epilepsy |
17 | WFS1 | tNGS | C/Het | c.874C>T & c.877del | 20 | Insulin | n/k | 21.8 | 42 | 24 | Bilateral optic atrophy, neurogenic bladder, diet treatment, muscle pain on exercise |
175 | POLD1 | Exome | Het | c.1812–1814del | 14 | OHA | No | 18.6 | 30 | 21 | Total lipodystrophy, sensorineural deafness, mandibular hypoplasia, hypogonadism, undescended testes, severe insulin resistance |
References for the genes and further details of the mutations are in Supplementary Table 3.
C/Het, compound heterozygous; Het, heterozygous; Hom, homozygous; Hp, Hp gene deletion; Ins, insulin; OHA, oral hypoglycemic agent; tNGS, targeted next-generation sequencing.