MODY (Maturity-Onset Diabetes of the Young) představuje nejčastější formu monogenního diabetu. Genetické testování českých pacientů s klinickým podezřením na MODY začalo před 22 lety. Cílem studie bylo shrnout dosavadní nálezy. Klinická kritéria pro genetické testování MODY jsou věk v době diagnózy hyperglykemie do 35 let a absence pankreatických protilátek. Mezi podpůrná kritéria pro dospělé pacienty, z nichž alespoň některé musí být splněno, patří: výskyt diabetu ve více po sobě jdoucích generacích, detekovatelný C peptid několik let po diagnóze či absence známek metabolického syndromu. V českém registru pacientů suspektních na MODY evidujeme 1 788 rodin (3 539 osob), z nichž byla diagnóza MODY geneticky prokázána u 1 385 osob z 686 rodin (38%). Převažujícím podtypem (69%) byl glukokinázový diabetes (GCK-MODY) diagnostikovaný u 962 osob ze 473 rodin. Druhým nejčastějším podtypem MODY (16%) byl HNF1A-MODY nalezený u 111 rodin (233 osob). HNF4A-MODY představoval třetí nejčastější podtyp MODY (131 osob z 60 rodin, 9%). Zbývajících 6% potvrzených případů MODY (42 rodin) byly vzácné formy monogenního diabetu. Stanovení správné diagnózy MODY je zásadní pro pacienty a jejich rodiny, protože s sebou přináší možnost optimalizované, personalizované léčby.
Maturity-Onset Diabetes of the Young (MODY) represents the most frequent form of monogenic diabetes. Genetic testing of Czech patients with clinical suspicion on MODY began 22 years ago. The aim of the study was to describe the overall findings. Clinical criteria for genetic testing of MODY genes include age at diagnosis up to 35 years and absence of pancreatic antibodies. Supporting criteria, of which at least some must be fulfilled in adult probands, are positive family history of diabetes, detectable C-peptide several years after diagnosis and absence of metabolic syndrome. The Czech registry of MODY consists of 1,788 families (3,539 persons) of which MODY has been genetically clarified in 1,385 patients from 686 families (38%). Glucokinase diabetes (GCK-MODY) was the prevailing MODY subtype (69%) being diagnosed in 962 subjects from 473 families. The second most prevalent MODY subtype (16%) was HNF1A-MODY detected in 111 families (233 persons). HNF4A-MODY represented the third most prevalent subtype (131 persons, 60 families, 9%). The remaining 6% (42 families) of confirmed MODY represented rare forms of monogenic diabetes. Assessment of correct diagnosis of MODY is crucial for the patients and their families because it brings along tailored treatment options.
- Publikační typ
- abstrakt z konference MeSH
AIMS: We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. METHODS: A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent's perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. RESULTS: Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p<0.001). QoL was better in patients with HNF-MODY compared with patients with T1D (p=0.006), and they did not differ in terms of treatment satisfaction. CONCLUSIONS: QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.
- MeSH
- diabetes mellitus 1. typu psychologie terapie MeSH
- diabetes mellitus 2. typu psychologie terapie MeSH
- dítě MeSH
- dospělí MeSH
- kvalita života * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- spokojenost pacientů * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
AIMS: Correct genetic diagnosis of maturity-onset diabetes of the young (MODY) is beneficial for person's diabetes management compared to no genetic testing. Aim of the present study was a search for optimal time- and cost-saving strategies by comparing two approaches of genetic testing of participants with clinical suspicion of MODY. METHODS: A total of 121 consecutive probands referred for suspicion of MODY (Group A) were screened using targeted NGS (tNGS), while the other 112 consecutive probands (Group B) underwent a single gene test based on phenotype, and in cases of negative findings, tNGS was conducted. The study was performed in two subsequent years. The genetic results, time until reporting of the final results and financial expenses were compared between the groups. RESULTS: MODY was confirmed in 30.6% and 40.2% probands from Groups A and B, respectively; GCK-MODY was predominant (72.2% in Group A and 77.8% in Group B). The median number of days until results reporting was 184 days (IQR 122-258) in Group A and 91 days (44-174) in Group B (p < 0.00001). Mean costs per person were higher for Group A (639 ± 30 USD) than for Group B (584 ± 296 USD; p = 0.044). CONCLUSIONS: The two-step approach represented a better strategy for genetic investigation of MODY concerning time and costs compared to direct tNGS. Although a single-gene investigation clarified the diabetes aetiology in the majority of cases, tNGS could reveal rare causes of MODY and expose possible limitations of both standard genetic techniques and clinical evaluation.
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- gen PROP1,
- MeSH
- efekt zakladatele MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- homeodoménové proteiny genetika MeSH
- hypofyzární hormony * nedostatek MeSH
- hypopituitarismus genetika MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- mutace * genetika MeSH
- mutační analýza DNA MeSH
- prevalence MeSH
- transkripční faktor Pit-1 genetika MeSH
- Check Tag
- lidé MeSH
- MeSH
- endokrinologie * MeSH
- odměny a ceny MeSH
- Publikační typ
- autobiografie MeSH
- O autorovi
- Dušátková, Petra, 1983- Autorita
Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
