Autosomal Dominant Type Of Inheritance Research Articles

New allelic variants of non-syndromic mental retardation of type 20 caused by mutations in the MEF2C gene

To determine clinical and genetic characteristics of patients with non-syndromic mental retardation (NMR), type 20 with autosomal dominant type of inheritance (OMIM: 613443). Fourteen patients were studied including four patients with mutations in the MEF2C gene revealed by exome sequencing. Three of the four mutations in the gene were found for the first time. Based on a comparative analysis of the clinical manifestations of 4 observed patients and 9 patients with type 20 NMR described in the literature, the authors determined common clinical characteristics of this syndrome. In most cases with delayed psycho-speech development and convulsive syndrome, the patients were expected to have various variants of early epileptic encephalopathies, in which presence of convulsive paroxysms leads to intellectual deficit, while in the case of NMR, the delay in development can be noted long before the onset of seizures. Exome sequencing is the most effective method of NMR diagnosis.

Monogenic diabetes associated with PAX4 gene mutations (MODY9): first description in Russia

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 13. MODY2 and MODY3 are the most prevalent subtypes, and were previously described in our country, Russia. Several cases of rare MODY subtypes were subsequently described in the Russian literature. The current report is the first in the Russian literature to present clinical and molecular genetic characteristics of two cases of another rare MODY subtypeMODY9. This type of MODY is associated with mutations in the PAX4 gene, which encodes transcription factor PAX4, one of the factors essential for pancreatic beta-cell differentiation. Molecular genetic analysis was performed using next-generation sequencing, a new method recently applied to verify monogenic diseases and, in particular, MODY. This study reports a novel mutation in the PAX4 gene in MODY patients.

Acute debut of neuroacanthocytosis in clinical practice

Neuroacanthocytosis is a rare autosomal dominant disease, which in its clinical manifestation is characterized by choreiform hyperkinesis, mental and cognitive disorders, signs of polyneuropathy and cardiomyopathy, and the basis of the disease is presence of modified erythrocytes (acanthocytes) in peripheral blood. The disease is characterized by autosomal dominant type of inheritance (the gene was mapped on chromosome 9q21), sporadic cases are possible. Description of a clinical case of a 63-year old patient with neuroacanthocytosis delivered by an ambulance with a preliminary diagnosis of stroke is provided. The patient complained of severe general fatigue, whole body shivering, and involuntary compulsive uncontrollable movements in the limbs, body, and face. The patient noted changes in her voice, probably due to compulsive movements of her tongue, lightheadedness, and shaky walk. Almost all physical and laboratory findings were within normal. Taking into account acuteness of the disease, its attack at the time of hypertensive emergency and patient’s age, circular cause was suggested, computed tomography of the brain and magnetic resonance imaging were performed. The results of neuroimaging ruled out the pathology of cerebral circulation. Ultrasound of neck vessels revealed nothing abnormal. Purposeful repeated blood analysis revealed that 85% of erythrocytes were acanthocytes and after that the correct diagnosis was made. The peculiarities of this clinical case are acute manifestation of symptoms and relatively late debut of the disease.

Hereditary variant of diabetes mellitus caused by a defect of the NEUROD1 gene (MODY6): the first description in Russia

MODY (Maturity-Onset diabetes of the young) is a heterogeneous group of disorders characterized by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic b-cells. Currently 13 candidate genes of MODY, and, respectively, 13 MODY subtypes are known. The final diagnosis can be established only on the basis of molecular genetic studies, which is the «gold standard» in the diagnosis of this disease. MODY2 and MODY3 are the most prevalent subtypes and were previously described in our country. Rare MODY subtypes have not been described in Russian literature. In this article we describe the first diagnosed case of MODY6 in Russia (a defect of the NEUROD1 gene, encoding neurogenic differentiation factor 1, which plays an important role in normal differentiation of β-cells of the pancreas and the regulation of transcription of the insulin gene). Molecular genetic study was conducted using the method of next-generation sequencing, has recently been widely used for genetic verification of monogenic diseases and, in particular, MODY. Technology of next-generation sequencing for diagnosing inherited disorders of carbohydrate metabolism in domestic practice used for the first time.

Differentiating tremor patients using spiral analyses.

Essential tremor follows an autosomal dominant type of inheritance in the majority of patients, yet its genetic basis has not been identified. The age of onset in this tremor is bimodal, one in young age and another when they are old. The old onset is referred to as senile tremor in this study. The precise pathology is still not completely understood for both these tremors. We wanted to develop an easy diagnostic tool to differentiate these two tremors clinically. In this study, the spirals were asked to be drawn by 30 patients, 15 from each group. The spirals were recorded digitally from each hand, with and without the spiral template, using a Wacom intuos version 4 tablets. The aim of the study was to look at the easy diagnostic measures from these spirals to distinguish the two cohorts of patients. The first measure was to use the well-known clinical scores like the number of complete circles without the template, width, height, axis, and degree of severity. The second measure was to estimate the peak frequency and the peak amplitude for the position, velocity, and acceleration data, in the frequency domain. The well-known clinical scores, most of them, did not show any significant difference between the two patient cohorts except the degree of severity which showed significant difference. The peak frequency and the peak amplitude in most of the data were not significantly different between the two cohorts of patients, only the peak amplitude from the acceleration data showed significant difference. Thus, we could use these two parameters to differentiate between the two tremors patient groups, which would be an easy clinical diagnostic tool without the need for any complicated analyses.

A familial case of segregation of motor sensory neuropathy type 1B with multiple exostoses in monozygous twins

Hereditary motor-sensory neuropathy (MIM 118200) is a rare genetic variant of myelinopathy with autosomal-dominant type of inheritance. Multiple exostosis bones are signs of multiple exostoses chondrodysplasia, genetically heterogeneous form of systemic bone disease with an autosomal dominant mode of inheritance. The combination of two rare autosomal dominant diseases, affecting bone and peripheral nervous system in a pair of monozygotic twins and their father in one family, belongs to a unique clinical observations: since early childhood twins presented sharp reduction of the conduction velocity in all investigated motor nerves (>10 times) together with multiple exostosis bone, confirmed by x-ray with a relatively benign course. Similar manifestations were detected in the patients father. DNA analysis confirmed the presence of 2 separate mutations in 2 different genes, с.389А>G/N gene MPZ and c.678С>А/N EXT2 gene that was inherited autosomal dominant manner, independently of each members of the same family.

The Importance of Clinical Genotype in Patients with Klinefelter Syndrome. A Genetic Disorder Asociated to Taurodontism

Taurodontism is a clinical condition found in the molar teeth of humans whereby the body of the tooth and pulp chamber is enlarged vertically at the expense of the roots. As a result, the floor of the pulp and the furcation of the tooth is moved apically down the root. It is due to the failure or late invagination of Hertwig’s epithelial root sheath, which is responsible for root formation and shaping causing an apical shift of the root furcation. The constriction at the amelocemental junction is abnormally formed. Taurodontism is most commonly found in permanent dentition although the term is traditionally applied to molar teeth. It has been reported that taurodontism follows an autosomal dominant type of inheritance. Meanwhile, Mutations or chromosome aberrations are considered alterations in the chromosome number or structure. They are mainly considered due to gametogenesis inborn error at meiosis, where DNA loses are seen due to DNA repair processes deficiency. Some chromosome studies were performed were 34.6% (1596 patients) showed different chromosome alterations. Among the studies population, male and female pediatric patients with sexual genetic diseases were chosen. These chromosome changes are classified as numeric or structural alterations, respectively. A wide variety of pediatric patients with genetic diseases chromosome alterations are described in this study analyzing their clinical characteristics, medical, surgical treatments and their clinical evolution according to the genetic disease.

Corticomuscular coherence in asymptomatic first‐degree relatives of patients with essential tremor

Essential tremor (ET) follows an autosomal dominant type of inheritance in the majority of patients, yet its genetic basis has not been identified. Its exact origin is still elusive, but coherence measurements between electromyography tremor bursts and electroencephalography unequivocally demonstrate a correlation. We tested these measurements in 37 healthy first-degree relatives (children) of patients with essential tremor (ET) and a group of 37 age-matched and sex-matched controls. Pooled coherence spectra of the maximally coherent electroencephalogram electrodes were computed for ET relatives and controls. The maximal coherence and its frequency were significantly higher in ET relatives than in controls during the pinch grip task and during slow hand movements. Electromyography amplitude (root-mean-square) was slightly but significantly greater in ET relatives, whereas 2-Hz to 40-Hz power and spectral peak frequency were not different. The presymptomatic alteration in corticomuscular interaction may reflect a role of genetic factors.

Dupuytren's Contracture Cosegregation with Limb-Girdle Muscle Dystrophy

Limb-girdle muscular dystrophies (LGMDs) is a heterogeneous group of muscular dystrophies that mostly affect the pelvic and shoulder girdle muscle groups. We report here a case of neuromuscular disease associated with Dupuytren's contracture, which has never been described before as cosegregating with an autosomal dominant type of inheritance. Dupuytren's contracture is a common disease, especially in Northern Europe. Comorbid conditions associated with Dupuytren's contracture are repetitive trauma to the hands, diabetes, and seizures, but it has never before been associated with neuromuscular disease. We hypothesize that patients may harbor mutations in genes with functions related to neuromuscular disease and Dupuytren's contracture development.

Organization experience of diagnostic and medicosocial services for patients with Charcot—Marie—Tooth disease in Krasnoyarsk region

Hereditary neuropathy Charcot-Marie-Tooth (CMT) is the most common form of hereditary polyneuropathies. Goal of the study was the development of evidence-based diagnostic and treatment algorithms using patients with CMT (for example, in Krasnoyarsk Territory). Materials and methods: A total of 324 people. (probands and their relatives 1 and 2 lines of kinship). We analyzed 125 (38,5 %) clinical cases of CMT, 64/125 (51,2 %) clinical cases were include to statistical analysis (probands and their family trees, past the full range of clinical and laboratory findings according to the protocol this study). Age ranged from 6 to 81 years, median age — 30,5 years, including women 24 (37,5 %), median age — 33,5 years; males 40 (62,5 %), median age — 28,5 years. Methods of diagnosis: clinical, genetic, neurophysiological, molecular genetic, assessment of quality of life assessment of anxiety and depression. Results: The family history of CMT noted in 53/57 (93,0 %) cases, with a predominance of autosomal dominant type of inheritance — 52 (91,2 %) cases. As a result of DNA testing duplication of peripheral myelin protein gene (RMR22) on chromosome 17, held 34 survey, this mutation was found in 17 (50,0 %) patients. Modified method of computer esthesiometry for CMT diagnosis using domestic diagnostic equipment “Vibrotester-MBN” BT-02-1 has a high sensitivity in the early stages of the disease and can be recommended for more widespread adoption of on par with other subjects of the Russian Federation.

Type 2 diabetes can also be multigenerational like MODY

Type 2 diabetes (T2DM) is now known to comprise of a heterogeneous group of metabolic disorders. The common garden variety of T2DM with onset in adult life is a multifactorial or polygenic disorder with multiple genes each playing a relatively minor role towards the overall risk of T2DM [1]. In addition, there is a large environmental component. Familial aggregation of T2DM is well known, and up to 40–60% of T2DM patients may have a family history of diabetes in a first degree relative [2]. This figure would obviously be higher if all the relatives were screened for diabetes rather than based on ‘known’ family history of diabetes. Multigenerational diabetes, with an autosomal dominant type of inheritance, is common in the monogenic forms of diabetes like Maturity Onset Diabetes of the Young (MODY) [3, 4]. Patients with MODY, typically have a diabetic parent and a grandparent, and often a great grandparent on the affected parent’s side with diabetes, suggestive of autosomal dominant inheritance [5]. MODY type diabetes, is now classified into at least 6 distinct types (MODY-1 to MODY-6) based on the specific genetic mutation involved, although newer MODY types continue to be described [6, 7]. MODY 3 (due to HNF1- ∝ mutations) is the commonest form of MODY followed by MODY-1 (due to HNF-4 ∝ mutations) and together they are believed to comprise up to 75% of adult onset MODYamong Europeans [3, 4, 6]

Analysis of the α-synuclein gene dosage variation associated with autosomal dominant form of Parkinson’s disease

Fifty-two patients that had ParkinsonTs disease with autosomal dominant type of inheritance were analyzed for the presence of duplications and triplications in exons 4--6 of alpha-synuclein gene using real-time PCR with Taq-Man probes. No mutations involving the examined exons dosage were revealed in alpha-synuclein gene. Thus, mutations modifying copy number of alpha-synuclein gene do not significantly affect the pathogenesis of the autosomal dominant form of ParkinsonTs disease in patients from Russia.

The diagnosis and treatment of hereditary forms of medullary carcinoma of the thyroid: Clinical and genetic aspects

Medullary thyroid cancer (MTC) is a fairly rare disease, accounting for 5-7% of all cases of thyroid cancer. The sporadic form of thyroid cancer is observed in 70-80% of cases, family (inherited - autosomal dominant type of inheritance) - in 20-30%. Familial forms of MTCG are caused by point mutations in the RET proto-oncogen (Rearranged during Transfection). To date, about 25 germinal (inherited) mutations are described in the world literature in 19 codons of the RET gene, which are found in 97% of patients with MEN 2A, in 95% with MEN 2B and in 86% of patients with SMR.

Familial Non Medullary Thyroid Cancer*

When one thinks about patients with familial thyroid cancer, one usually considers familial medullary thyroid cancer or perhaps familial thyroid cancers associated with familial polyposis or Cowden’s syndromes. However, there have been an increasing number of articles regarding patients with FNMTC in the past few years [1-16]. Familial non medullary thyroid cancer (FNMTC) without any other associated syndrome, however, accounts for about 5% of patients with thyroid cancer of follicular cell origin (prevalence ranges between 3.5 and 6.2%) [1, 17, 18]. FNMTC has been defined as families with two or more first degree relatives having cancer papillary or Hurthle cell thyroid. In patients with three or more members with thyroid cancer there appears to be an autosomal dominant type of inheritance with incomplete penetrance and 99.9% of these patients have familial disease [2]. Patients with FNMTC also are more likely to have other thyroid pathology including multinodular goiter as well as other non thyroid cancers [3]. When two members of a family have thyroid cancer some will have a susceptibility gene for thyroid cancer; the others may have sporadic non familial tumors [2].

Familial Bilateral Optic Nerve Hypoplasia

Bilateral optic nerve hypoplasia affected five individuals corresponding to four generations of a family. Two decreased men were also apparently affected. The three patients studied, two women and a girl, presented the same clinical picture: poor visual acuity; small, pale and malformed papilla; two concentric peripapillary halos; and wandering movements of the eyes. Fluorescein angiography performed in the propositus mother showed a faint papillary fluorescence. At variance with the two familial cases reported, the pedigree clearly suggest an autosomal dominant type of inheritance. Similar clinical features found in other patients suggest a stationary nature of the defect.

Familial muscular dystrophy of late onset.

Two related cases of a proximal muscular dystrophy are described with the full postmortem findings in one of them. The strong family history is recorded. The condition was clinically predominant in the proximal limb muscles and showed an autosomal dominant type of inheritance with complete penetrance.

CHROMOSOME PATTERNS IN IRRADIATED AND NONIRRADIATED PATIENTS WITH RHEUMATOID SPONDYLITIS.

Article1 December 1963Chromosome Patterns in Irradiated and Nonirradiated Patients with Rheumatoid SpondylitisDAVID S. NEWCOMBE, M.D., ALAN S. COHEN, M.D.DAVID S. NEWCOMBE, M.D.Search for more papers by this author, ALAN S. COHEN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-6-859 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince the introduction of relatively simple and specific methods for the analysis of human chromosomes, studies of heritable or genetically determined disorders have been extensive. Rheumatoid spondylitis would appear to be an appropriate disorder for such chromosome analyses for several reasons. First, there are indications that genetic mechanisms may play a role in its etiology, that is, the strong tendency toward the familial occurrence of spondylitis, the apparently autosomal dominant type of inheritance with incomplete penetrance, and the appearance of the disorder in twins (1). Second, X-irradiation, now associated with a documented increased incidence of leukemia (2), has been used...

Eight Cases of Hereditary Bilateral Medial Tibial Torsion in Four Generations

Multiple marriages in this pedigree strengthen the evidence of a genetic basis for the inheritance of torsion. The apparent progenitor (I-1) was married twice, transmitting the abnormality to offspring of both marriages. Two later marriages of the mate of II-1 substantiate this conclusion, since none of the progeny of these two unions show the trait. Examination of Chart I reveals that only those individuals possessing the trait transmit it to their offspring; that the trait manifests itself in every generation; that approximately one-half of the total number of individuals in the family are affected; and that the abnormality affects males and females alike. A Mendelian autosomal dominant type of inheritance is demonstrated for bilateral medial tibial torsion in this pedigree.