scholarly journals Clinical, Genetic and Orthopedic Characteristics of Desbuquois Dysplasia

2021 ◽  
Vol 27 (3) ◽  
pp. 71-83
Author(s):  
Tatyana V. Markova ◽  
Vladimir M. Kenis ◽  
Evgeniy V. Melchenko ◽  
Peter A. Sparber ◽  
Marina S. Petukhova ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Clinical Manifestations ◽  
Genetic Data ◽  
Congenital Glaucoma ◽  
Ossification Center ◽  
Renal Hypoplasia ◽  
Desbuquois Dysplasia ◽  
Joint Dislocations

Introduction. Desbuquois dysplasia is a rare skeletal dysplasia with an autosomal recessive inheritance, resembling to the group of multiple joint dislocations. The disease is caused by mutations in the CANT1 and XYLT1 genes, the protein products of which are involved in the degradation of proteoglycans, which play an important role in endochondral ossification. The polymorphism of clinical and radiological characteristics and the genetic heterogeneity of Desbuquois dysplasia necessitate the description of the phenotypic characteristics of patients with various types of mutations, which optimize diagnosis. Objective description of the clinical and radiological characteristics of three Russian patients with Desbuquois dysplasia of types 1 and 2 with remarkable orthopedic manifestation, caused by mutations in the CANT1 and XYLT1 genes. Materials and Methods. Genealogical, clinical, radiographic and genetic data of three unrelated Russian patients aged 2 to 8 years was carried out. Genetic testing was carried out using clinical exome sequencing and methyl-sensitive PCR. Results. Two patients were diagnosed with type 1 disease due to a previously described homozygous mutation in the CANT1 gene: c.898CT (p.Arg300Cys), and one type 2 due to heterozygous mutations in the XYLT1 gene. One mutation: c.1651CT (p.Arg551Cys) was detected during exome sequencing, and the second mutation: expansion of GGC repeats in the promoter region of the gene, revealed by methyl-sensitive PCR of the first exon of the gene. The main clinical signs of the disease were micromelic dwarfism, hypermobility in the joints and specific facial dysmorphisms, radiographic analysis revealed characteristic monkey wrench appearance of the proximal femur in all 3 patients, additional ossification center of the second metacarpal, advanced bone age and multiple dislocations in the joints. The patients also had extra-skeletal manifestations (congenital glaucoma, obstructive bronchitis, renal hypoplasia and congenital heart malformations). Conclusion. Genetic heterogeneity and the presence of polymorphism of clinical manifestations make it possible to consider sequencing of the clinical exome as the optimal method for diagnosing Desbuquois dysplasia types 1 and 2. Analysis of the literature and the results of our molecular genetic data indicate the possibility of expansion of the GGC repeat in the XYLT1 gene in patients with clinical manifestations of type 2 Desbuquois dysplasia.

scholarly journals Radiographic findings of Desbuquois dysplasia

2020 ◽  
pp. 20200137
Author(s):  
Meltem Özdemir ◽  
Rasime Pelin Kavak
Keyword(s):  
Radiographic Finding ◽  
Ossification Center ◽  
Radiographic Findings ◽  
Desbuquois Dysplasia ◽  
Joint Dislocations ◽  
Almost All ◽  
Femoral Bowing ◽  
Skeletal Findings

Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint laxity, progressive scoliosis, and advanced carpotarsal ossification. Two different types of Desbuquois dysplasia have been identified according to the presence (Type 1) or absence (Type 2) of characteristic hand abnormalities including bifid distal thumb phalanx, an extra ossification center distal to the second metacarpal, and interphalangeal joint dislocations. Further, Kim et al have described a milder variant of Desbuquois dysplasia characterized by short stature and hands with short metacarpals, elongated proximal and distal phalanges, and extremely advanced carpal ossification. Here, we present a 19-year-old male patient with Kim variant of Desbuquois dysplasia. He displays almost all of the characteristic skeletal findings of Desbuquois dysplasia along with the characteristic hand features described by Kim et al. This patient is unique in that he also presents sagittal femoral bowing, a radiographic finding that accompanies various skeletal dysplasias but has never been reported in a patient with Desbuquois dysplasia to date.

Diastrophic Dysplasia and Related Conditions, and Dysplasias with Joint Dislocations

2018 ◽  
pp. 245-306
Author(s):  
Jürgen W. Spranger ◽  
Paula W. Brill ◽  
Christine Hall ◽  
Gen Nishimura ◽  
Andrea Superti-Furga ◽  
...  
Keyword(s):  
Clinical Findings ◽  
Joint Laxity ◽  
Diastrophic Dysplasia ◽  
Desbuquois Dysplasia ◽  
Recessive Type ◽  
Joint Dislocations ◽  
Bone Dysplasias ◽  
Epiphyseal Dysplasia ◽  
Spondyloepimetaphyseal Dysplasia

This chapter further discusses bone dysplasias and includes discussion on achondrogenesis (type IB), atelosteogenesis type 2, diastrophic dysplasia, multiple epiphyseal dysplasia (recessive type [rMED]), Desbuquois dysplasia, chondrodysplasia with joint dislocations (IMPAD1/gPAPP type), Catel-Manzke syndrome, chondrodysplasia with congenital joint dislocations (CHST3-type), temtamy preaxial brachydactyly syndrome (TPBS), B4GALT7 deficiency, B3GAT3 deficiency, XYLT1 deficiency, spondyloepimetaphyseal dysplasia with joint laxity Beighton type, spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type), pseudodiastrophic dysplasia, and Steel syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.

Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency

2016 ◽  
Vol 61 (7) ◽  
pp. 577-583 ◽  
Author(s):  
Aleksander Jamsheer ◽  
Ewelina M Olech ◽  
Kazimierz Kozłowski ◽  
Marek Niedziela ◽  
Anna Sowińska-Seidler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Exome Sequencing ◽  
Hormone Deficiency ◽  
Compound Heterozygous ◽  
Desbuquois Dysplasia ◽  
Polish Patient

scholarly journals Facial cleft? The first case of manitoba‐oculo‐tricho‐anal syndrome with novel mutations in China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuchen Gu ◽  
Yimin Khoong ◽  
Xin Huang ◽  
Tao Zan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestations ◽  
Sporadic Case ◽  
Facial Cleft ◽  
Ocular Manifestations ◽  
First Case ◽  
Whole Exome ◽  
Chinese Girl ◽  
Low Prevalence

Abstract Background Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing. Case presentation A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established. Conclusions We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.

scholarly journals Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure

2009 ◽  
Vol 161 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Anne Bachelot ◽  
Agnès Rouxel ◽  
Nathalie Massin ◽  
Jérome Dulon ◽  
Carine Courtillot ◽  
...  
Keyword(s):  
Premature Ovarian Failure ◽  
Chromosomal Abnormalities ◽  
Phenotypic Variability ◽  
Genetic Data ◽  
Ovarian Failure ◽  
Mineral Density ◽  
Genetic Studies ◽  
Autoimmune Polyendocrine Syndrome ◽  
Design And Methods

ObjectivePremature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis.Design and methodsWe performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center.ResultsSeventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1.ConclusionA genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

Clinical and pathogenetic features of intestinal lesions in patients with type 2 diabetes mellitus

2021 ◽  
Author(s):  
Y. Z. Dynia
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Clinical Manifestations ◽  
Intestinal Damage ◽  
Hydrogen Breath Test

Objective — to study the incidence and clinical and pathogenetic features of intestinal injury in patients with type 2 diabetes mellitus. Materials and methods. Examinations involved 138 patients with type 2 diabetes mellitus (DM 2), aged from 39 to 67 years (mean age 53 ± 5 years), including 82 women (59 %) and 56 men (41 %). In addition to general clinical methods, investigations included plasma levels of the transforming growth factor‑b1 (TGF‑b1) and vascular endothelial growth factor (VEGF), the hydrogen breath test with lactulose, endoscopic examination of the intestine with biopsy followed by staining with hematoxylin‑eosin, immunohistochemical determining of claudin‑1 and VEGF, and conduction of PAS‑reaction. Results. Diabetic enterocolopathy (DECP) was diagnosed in 72 (52.2 %) patients with DM 2. Clinical manifestations were nonspecific and similar to those of irritable bowel syndrome (IBS). It has been found that DECP correlates with the duration of the DM 2 course and was diagnosed more often in middle‑aged patients (52.1 ± 4.1 years). In patients with DECP, the increase in the proinflammatory cytokines TGF‑b1 and VEGF significantly exceeded those in IBS patients. Histologically the inflammatory cell infiltration in patients with DECP was more intense and diverse, there were signs of subatrophy of the glands with a relative decrease in the number of vacuoles in the goblet cells. The immunohistochemical study revealed that VEGF in the colon mucosa was visualized mainly in patients with DECP. Moreover, a tendency to a decrease in the claudin‑1 levels was established in these patients. Conclusions. Intestinal damage was revealed in 67.4 % of patients with type 2 diabetes mellitus, and DECP was diagnosed in more than half of patients. Diabetic enterocolopathy had nonspecific clinical symptoms, required differential diagnosis with IBS, and was not always accompanied with abdominal pain. The presence of DECP more often correlated with the bacterial overgrowth syndrome, and levels of proinflammatory cytokines in the blood plasma and intestinal mucosa of these patients was raised.  

scholarly journals Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109178 ◽  
Author(s):  
Jie Qing ◽  
Denise Yan ◽  
Yuan Zhou ◽  
Qiong Liu ◽  
Weijing Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Chinese Family ◽  
Whole Exome

scholarly journals Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity

Cell Reports ◽  
2018 ◽  
Vol 25 (6) ◽  
pp. 1446-1457 ◽  
Author(s):  
Weiwei Shi ◽  
Charlotte K.Y. Ng ◽  
Raymond S. Lim ◽  
Tingting Jiang ◽  
Sushant Kumar ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome

scholarly journals A Critical Review on Clinical Manifestations of Obesity in Type 2 Diabetes Mellitus and Solution through Physical Activity

2021 ◽  
pp. 88-93
Author(s):  
Charu Bansal ◽  
Rachna Jain ◽  
Umesh Shukla ◽  
Smita Paul
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Clinical Manifestations ◽  
World Health ◽  
Health Organization ◽  
And Control ◽  
Published Research ◽  
Healthy Behaviour

Diabesity term recently coined in medical field because of the very close epidemiological and pathogenic associations between central obesity and Type 2DM. Material and Methods: This review is based on data collected from published research works in various journals. Observations and Results: cited based on research reviews to find out risk odds of obesity and physical inactivity and initiation of type 2 diabetes with solutions based on improve physical activity. Conclusion: Counseling would be one of the best strategies to opt physical exercise with moderate and vigorous intensity recommended as world health organization as healthy behaviour to prevent and control of type 2 diabetes. Thus, Present write up is an effort to critically evaluate and assess the published research data on obesity and its association with development of type 2 diabetes and role of Physical exercises for prevention and control of type 2 DM as its solution with research evidences.

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