Background. Gestational diabetes (GDM) due to GCK gene mutations is the most frequent form of monogenic diabetes mellitus (DM) presenting during pregnancy. It has been suggested that the use of insulin in pregnancies with fetuses carrying GCK mutations may lead to intrauterine growth retardation. In the present study we evaluated the effect of insulin therapy during pregnancy on birth weight and length in the offsprings of mothers with GDM due to GCK mutations. Aims. The aim was to study birth weight and length in offsprings of mothers with gestational diabetes mellitus due to mutations in GCK, depending on the therapy during pregnancy. Materials and methods. The study included 38 patients with GDM caused by GCK gene mutations (18.7%) and the 45 offsprings. To define molecular basis of GDM in pregnant women we used a targeted NGS. Diabetes panel genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). To found the same mutations in their offsprings was used Sanger sequencing. All children were divided into 3 groups depending of their genotype and therapy received by the mothers during pregnancy. Results. We found statistically significant differences in birth length (p=0.04) and weight (p=0,031) depending on the genotype of the child and therapy in the mother. The risk of macrosomia was shown in non-mutation-carrying offsprings only. The birth weight in children with GCK gene mutations whose mothers received insulin during pregnancy was significantly lower. However, the birth weight remained in the normal range. Conclusions. Since prenatal diagnostics in the mothers with GCK gene mutations is not always justified, we recommend insulin therapy in order to prevent fetal macrosomia, which, however, should be less aggressive than in GDM due to other causes.
Approximately 90% of all cases of diabetes mellitus in adults involve type 2 diabetes, while the prevalence of maturity-onset diabetes of the young (MODY) remains undetermined leading to inappropriate treatment regimens. One of the most common monogenic forms of diabetes is a disease caused by a mutation in the glucokinase gene, MODY2. Knowledge of the clinical features of the disease allows the selection of patients with a high risk of mutation in the glucokinase gene and verification of diagnosis for molecular genetic research. This paper reflects the clinical features of MODY2 and the difficulties of diagnosis in adults. Furthermore, it presents a clinical case of a patient with MODY2 demonstrating all the features of this type of diabetes. A family member with a mutation in the gene allows to predict the nature of carbohydrate metabolism disorders in first degree relatives. A targeted study of only one part of the glucokinase gene in molecular genetic research is sufficient to confirm the diagnosis in relatives.
MODY1 and MODY3 represent rare causes of diabetes in pregnancy. Establishing a molecular diagnosis of MODY1 or MODY3 during pregnancy may be important for minimizing risk of perinatal complications and for improving glycemic control after pregnancy. The objective of the study was to evaluate the contribution of mutations in HNF4A and HNF1A genes in development of diabetes in pregnancy and to describe clinical characteristics of diabetes in pregnancy associated with these mutations. 230 pregnant women (20-43 years) with different type of glucose intolerance complicated during their current pregnancy were included in the study. A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. Heterozygous mutations in HNF4A and HNF1A genes were detected in 3% of cases. Mutations p.I271T in HNF4A gene and p.L148F, p.Y265C, p.G288W in HNF1A gene were novel. This study includes a description of patients with pregnancy diabetes due to mutations in hepatocyte nuclear factors.
CASE REPORT 384 | Сахарный диабет / Diabetes Mellitus ВВЕДЕНИЕИзучение молекулярных основ эндокринных заболева-ний является приоритетным направлением в эндокриноло-гии. Подтверждение моногенного характера заболевания позволяет четко регламентировать характер наблюдения пациента, назначить патогенетическую терапию и плани-ровать рождение здорового потомства. С 1974 г., когда впервые были описаны семьи с доминантно-наследуемым сахарным диабетом (СД), открыто около 30 генов, ответ-ственных за развитие моногенных форм диабета. Распро-страненность наследственных форм диабета активно изу-чается среди различных групп пациентов, прежде всего потому, что именно у этих больных возможна компенсация углеводного обмена без назначения инсулинотерапии. В конечном итоге это позволяет снизить расходы на обес-печение и лечение пациентов.Моногенные формы СД обусловлены, прежде всего, дефектами генов, регулирующих функцию β-клеток подже-лудочной железы (ПЖ), к которым относятся подтипы диа-бета MODY («maturity-onset diabetes of the young», «диабет зрелого типа у молодых»). Истинная распространенность 13 подтипов MODY, открытых к настоящему времени, не-известна. Большинство публикаций посвящено описанию мутаций в генах HNF1А, GCK и HNF4A, которые превали-руют среди MODY. Мутации в других генах-кандидатах Сахарный диабет типа MODY -генетически и клинически гетерогенная группа заболеваний, характеризующаяся аутосом но-доминантным типом наследования и обусловленная мутациями генов, приводящими к дисфункции β-клеток поджелудочной желе-зы. К настоящему времени верифицировано 13 подтипов MODY, наиболее распространенными из которых являются подтипы 1-3. MODY2 и MODY3 ранее неоднократно описаны в нашей стране. Описания более редких подтипов MODY в отечественной литературе единичны. В данной работе мы приводим клиническое и молекулярно-генетическое описание двух впервые выявленных в России случаев редкого подтипа MODY, обусловленного дефектом гена PAX4 (MODY9). Ген PAX4 кодирует фактор транскрипции PAX4, кото-рый участвует в дифференцировке β-клеток поджелудочной железы. Мутации в гене PAX4 приводят не только к нарушению развития β-клеток поджелудочной железы, но и снижению процессов их регенерации в последующей взрослой жизни. Молекулярно-генети-ческое подтверждение диагноза проведено с использованием технологии секвенирования нового поколения, позволяющей прово-дить одновременный анализ нескольких генов-кандидатов. Данная технология активно внедрена в последнее время в отечественную практику для генетической верификации моногенных заболеваний и, в частности, MODY. Найденные мутации ранее не описаны. Maturity-onset diabetes of the young (MODY) is a heterogeneous group of disorders characterised by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic beta-cells. To date, at least 13 subtypes of MODY have been described in the literature, the most frequent of which are MODY types 1-3. MODY2 and MODY3 are the most prevalent subtypes, and were previously described in our country, Russia. Seve...
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