Результаты поиска

Phenotypic Characterization of Seven Pediatric Patients Diagnosed With KAT6B -Related Disorders: Case Series and Review of the Literature.

Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson Syndrome (SBBYSS) are clinically distinct neurodevelopmental disorders caused by monoallelic pathogenic variants in KAT6B. In some cases, GPS and SBBYSS features can overlap, determining an intermediate phenotype. In the present study, we describe seven patients, four with a clinical diagnosis of SBBYSS and three presenting with an intermediate phenotype. All patients carried de novo pathogenic variants in KAT6B that were identified by exome sequencing. Five variants were novel. We provide both molecular and clinical findings

DEFENSIVE Stroke Scale: Novel Diagnostic Tool for Predicting Posterior Circulation Infarction in the Emergency Department.

BACKGROUND: Dizziness is the most common posterior circulation symptom; however, diagnosing a posterior circulation infarction is difficult due to a lack of typical symptoms. We aimed to investigate the frequency of misdiagnosis of a posterior circulation infarction in patients who presented with dizziness and to develop a new stroke scale that increased the diagnostic accuracy for stroke among these subjects. METHODS: We retrospectively analyzed consecutive data from subjects hospitalized with ischemic stroke who presented with dizziness (the developmental phase). Based on these results, we

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features

Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms.

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional p

Confirming the involvement of PIEZO2 in the etiology of Marden-Walker syndrome.

Pathogenic heterozygous variants in PIEZO2 typically cause distal arthrogryposis type 5 (DA5) and the closely related Gordon syndrome (GS). Only one case of PIEZO2-related Marden-Walker syndrome (MWS) has been reported to date. We report the phenotypic features of a Saudi female patient with features consistent with MWS in whom we identified a novel de novo likely pathogenic variant in PIEZO2. Our case lends support to the link between PIEZO2 and MWS.

Differentiating the Clinical and Variant Spectrum of Hardikar Syndrome From Other MED12 -Related Developmental Disorders.

The rare X-linked female-restricted Hardikar syndrome (HDKR, OMIM # 301068) is characterized by multiple congenital anomalies including orofacial clefts, gastrointestinal, genitourinary, and cardiac anomalies, but cognitive and neurobehavioral development is rarely impaired. HDKR is caused by heterozygous frameshift, splice or nonsense variants in the MED12 gene. Besides HDKR, MED12 pathogenic variants cause a broad spectrum of developmental disorders, collectively referred to as MED12-related disorders, including Opitz-Kaveggia syndrome or FG syndrome type 1 (OKS, OMIM #305450), Lujan-Fryns s

Congenital hydrocephalus in clinical practice: a genetic diagnostic approach.

Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Clinical Genetics between 1985 and 2010 by perinatologists, (child) neurologists or pediatricians. Patients with hydrocephalus secondary to other pathology were excluded from this survey. We classified patients with primary congenital hydrocephalus into two main groups: non-syndromic hydrocephalus (NSH

MED12 missense mutation in a three-generation family. Clinical characterization of MED12-related disorders and literature review.

Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12-related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, importan

MED12 Loss-of-Function Variants as a Cause of Congenital Diaphragmatic Hernia in Females With Hardikar Syndrome and Nonspecific Intellectual Disability.

Mediator complex subunit 12 (MED12) is required for the assembly of the kinase module of Mediator, a regulatory complex that controls the formation of the RNA polymerase II-mediated preinitiation complex. MED12-related disorders display unique gender-specific genotype-phenotype associations and include X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants, and X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de n

A Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome with a KAT6B 10-base pair palindromic duplication: A recurrent mutation causing a severe phenotype mixed with genitopatellar syndrome.

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation. Genotype-phenotype correlation is assumed, but a few patients manifest overlapping features of both syndromes. Here we report the case of a boy with SBBYSS. He had a KAT6B mutation previously reported in typical SBBYSS, but he also manifested severe developmental delay, as well as genital features and laryngomalacia requiring tracheostomy that conformed to GPS.

Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis.

We report ten individuals of four independent consanguineous families from Turkey, India, Libya, and Pakistan with a variable clinical phenotype that comprises arthrogryposis, spontaneously resolving respiratory insufficiency at birth, muscular atrophy predominantly of the distal lower limbs, scoliosis, and mild distal sensory involvement. Using whole-exome sequencing, SNPchip-based linkage analysis, DNA microarray, and Sanger sequencing, we identified three independent homozygous frameshift mutations and a homozygous deletion of two exons in PIEZO2 that segregated in all affected individuals

Clinical and neurocognitive characterization of a family with a novel MED12 gene frameshift mutation.

FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them. We report a family including 10 males and 1 female affected with profound non-specific intellectual disability (ID) which was linked to a 30-cM region extending from Xp11.21 (ALAS2) to Xq22.3 (COL4A5). Parallel sequencing of all X-chromosome exons identified a frameshift mutation (c.5898dupC) of MED12. Mutated mRNA was not affected by non-sense mediated

Mechanisms of premature ovarian failure.

The median age at menopause in Western populations of women is approximately 51 years. While very late (i.e., after 54 years) menopause is e … use POF, yet their prevalence has been difficult to determine. The localization of the gene for the blepharophimosis/ptosis/POF Syndrome has been recently reported, yet this finding has not been seen commonly in POF. Other genetic syndromes including POF await elucidation. Many transgenic "knock-out" animals have been created with deficient ovarian function. Most …

Vector control in internal midface distraction using temporary anchorage devices.

Le Fort III and monobloc distraction osteogenesis serve as the primary surgical treatment for children with severe midface hypoplasia. The orbital retrusion and class III malocclusion of patients with midface hypoplasia is best addressed with bodily advancement of the midface segment parallel to the cephalometric Frankfort horizontal plane. Use of internal distraction devices allows for advancement of the midface without extensive external hardware but comes at the cost of less vectorial control, resulting in a distraction vector that can cause a clockwise rotation of the entire midface or fro

Важное значение акромагалоидных физических свойств для клинической практики.

Акромагали и гигантизм - это гормональные расстройства, которые возникают в результате гиперсекретирования хронического роста гормона. Псевдоним префикса используется для описания определенного клинического состояния без четко подтвержденной характеристики патофизиологического механизма и основных биохимических характеристик; псевдоакромегалы или акромигалоидизм соответствуют определению, приведенному выше. В данном случае мы попытаемся представить краткий обзор диагностической оценки акромигалоидной физической внешности при обсуждении two - случаи пациентов, которые имеют такие же клинические

Совпадение в полном тексте источника
… He had deep nasolabial folds, bulbous nose, blepharophimosis, drooping of eyelids, and enlarged frontal bones. The teeth were spread apart and he had a very deep voice. The most important symptom was macroglossia, which caused his reduced quality of life. …

Exome sequencing confirms the clinical diagnosis of both joubert syndrome and klinefelter syndrome with keratoconus in a han Chinese family.

INTRODUCTION: Joubert syndrome a rare genetic disorder, is characterized by abnormalities in the development of the central nervous system w … sability, poor adaptive behavior, communication disorders, teeth all dentures, a peculiar face with blepharophimosis, wide inner canthus distance, mild ptosis, severe positive epicanthus, high palatal arches, exotropia, hypotrichosis of beard and face, inconspicuous prominentia laryngea, and short upper and lower limbs. Exome sequencing detected compound heterozyg …

Cancer in pregnancy: FIGO Best practice advice and narrative review.

Cancer during pregnancy is relatively rare. The incidence is underestimated due to the lack of international registries covering both high-income and low- and middle-income countries, and is expected to rise with increasing maternal age and increasing global adoption of cell-free DNA testing for aneuploidy. Physiological changes during pregnancy often make the diagnosis challenging and delayed. Lack of experience and knowledge about this condition may also contribute to late diagnosis, suboptimal management, and occasionally inadvertent fetal and/or maternal harm. The principles of cancer mana

Совпадение в полном тексте источника
… JCO Oncology Practice. 2020;16(9):545–557, with permission from Wolters Kluwer Inc. b Cyclophosphamide embryopathy phenotype: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly …

Rare Diseases of the Orbit.

This article provides an overview of rare orbital diseases. Congenital malformations, inflammatory diseases, benign and malignant neoplasias are described. Although it represents a relatively small area of the body the orbit contains multiple different tissues. Therefore, a great variety of diseases can be found within the orbital space. That is the reason, why both the completeness and the level of detail in the description of particular diseases must be somewhat limited. Nevertheless, clinical manifestations, important aspects of diagnosis, treatment strategies, and, when specific data are a

Совпадение в полном тексте источника
… axis of the eyelid, enophthalmos, lagophthalmos, pseudoptosis (differential diagnosis of associated Horner’s syndrome) exposed facial nerve in the middle ear atrophy of soft palate and tongue (speaking and swallowing disorders) saber-like scleroderma along the medial orbital skin heterochromia, blepharophimosis …

Резюме докладов 51st Конференция Европейского общества генетики человека: плакаты

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Abstracts from the World Congress of Cardiology/Brazilian Congress of Cardiology 2022

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.