scholarly journals Copy number variation in MODY diabetes - Familial case presentation

2018 ◽  
Vol 2 (2) ◽  
pp. 73
Author(s):  
Naida Lojo-Kadric ◽  
Zelija Velija Asimi ◽  
Jasmin Ramic ◽  
Ksenija Radic ◽  
Lejla Pojskic
Keyword(s):  
Insulin Secretion ◽  
Copy Number ◽  
Autosomal Dominant ◽  
Single Gene ◽  
Maturity Onset Diabetes ◽  
Dominant Form ◽  
Case Presentation ◽  
Monogenic Diseases ◽  
Number Variation ◽  
Autosomal Dominant Form

MODY (maturity-onset diabetes of the young) is an autosomal dominant form of diabetes that is usually manifested before the 25-year of life. This type of diabetes is caused by defects in the primary insulin secretion. There are several types of MODY, which are monogenic diseases, where mutations in a single gene are responsible for a particular type of MODY. Currently, there are eleven types of MODY, from which the most common types are MODY 2 and MODY 3 (with mutations on GCK and HNF1A genes, respectively). We identified very rare MODY 7 type of diabetes in three family members by MLPA analysis.

CADASIL Syndrome: A Genetic Form of Vascular Dementia

1998 ◽  
Vol 11 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Stephen Salloway ◽  
Joseph Hong
Keyword(s):  
Vascular Dementia ◽  
Autosomal Dominant ◽  
Microvascular Disease ◽  
The Elderly ◽  
Dominant Form ◽  
Genetic Features ◽  
Autosomal Dominant Form ◽  
Family Gene ◽  
Cerebral Arteriopathy ◽  
Genetic Form

Mental disorders due to cerebral microvascular disease have been known for over 100 years. Recently, an autosomal dominant form of cerebral arteriopathy (CADASIL) has been described in association with a Notch3 family gene on the short arm of chromosome 19. CADASIL causes subcortical lacunar infarction and dementia in over 80% of cases and depression in a large proportion of patients. Clinically, CADASIL may appear to be very similar to hypertensive microvascular disease (Binswanger's disease), a condition that is seen in the elderly. This article reviews the clinical, pathologic, and genetic features of CADASIL. CADASIL is of interest to neurologists and psychiatrists because it is the first syndrome of vascular dementia and depression with an identified gene. How the gene causes the widespread arteriopathy is not yet known. Insights gained from the study of CADASIL should help us better understand its etiology, as well as the options for treatment of the more common forms of microvascular disease seen in the elderly.

scholarly journals A New Locus on Chromosome 12p13.3 for Pseudohypoaldosteronism Type II, an Autosomal Dominant Form of Hypertension

2000 ◽  
Vol 67 (2) ◽  
pp. 302-310 ◽  
Author(s):  
Sandra Disse-Nicodème ◽  
Jean-Michel Achard ◽  
Isabelle Desitter ◽  
Anne-Marie Houot ◽  
Albert Fournier ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Type Ii ◽  
Dominant Form ◽  
Pseudohypoaldosteronism Type Ii ◽  
Autosomal Dominant Form ◽  
Pseudohypoaldosteronism Type

scholarly journals Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis

Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 2953-2960 ◽  
Author(s):  
P Savvides ◽  
O Shalev ◽  
KM John ◽  
SE Lux
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Autosomal Dominant ◽  
Hereditary Spherocytosis ◽  
Band 3 ◽  
Normal Range ◽  
Dominant Form ◽  
Autosomal Dominant Form ◽  
The Common ◽  
Ankyrin Deficiency

Abstract The common autosomal dominant form of hereditary spherocytosis (HS) has been genetically linked to defects of the erythroid ankyrin gene in a few families; however, the frequency of ankyrin deficiency and its relationship to red blood cell (RBC) spectrin content are unknown. To test these questions, we measured RBC spectrin and ankyrin by radioimmunoassay in 39 patients from 20 families with dominant HS. Normal RBCs contained 242,000 +/- 20,500 spectrin heterodimers and 124,500 +/- 11,000 ankyrins per cell. In dominant HS, RBC spectrin and ankyrin ranged from about 40% to 100% of normal and were continuously distributed. Measurements in the same patient on different occasions were reproducible (+/- 5% to 10%) and RBCs from affected members of a kindred contained similar amounts of spectrin and ankyrin (+/- 3% to 4%). Spectrin and ankyrin levels were almost always less than the assay controls, but were less than the normal range in only 75% and 80% of kindreds, respectively. Remarkably, the degree of RBC spectrin and ankyrin deficiency was very similar in 19 of 20 HS kindreds. One otherwise typical family differed, with marked ankyrin deficiency (45% of control) and a relatively mild spectrin deficit (81%). We conclude that most patients with dominant HS have combined ankyrin and spectrin deficiency and that the two proteins are usually about equally deficient, suggesting that defects in ankyrin expression, ankyrin stability, or ankyrin band 3 (AE1) interactions may be common in dominant HS.

BRCA Testing by Single-Molecule Molecular Inversion Probes

2017 ◽  
Vol 63 (2) ◽  
pp. 503-512 ◽  
Author(s):  
Kornelia Neveling ◽  
Arjen R Mensenkamp ◽  
Ronny Derks ◽  
Michael Kwint ◽  
Hicham Ouchene ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Copy Number Variation ◽  
Single Molecule ◽  
Copy Number ◽  
Single Gene ◽  
Work Flow ◽  
Analytical Sensitivity ◽  
Brca1 And Brca2 ◽  
Number Variation ◽  
Molecular Inversion Probes

Abstract BACKGROUND Despite advances in next generation DNA sequencing (NGS), NGS-based single gene tests for diagnostic purposes require improvements in terms of completeness, quality, speed, and cost. Single-molecule molecular inversion probes (smMIPs) are a technology with unrealized potential in the area of clinical genetic testing. In this proof-of-concept study, we selected 2 frequently requested gene tests, those for the breast cancer genes BRCA1 and BRCA2, and developed an automated work flow based on smMIPs. METHODS The BRCA1 and BRCA2 smMIPs were validated using 166 human genomic DNA samples with known variant status. A generic automated work flow was built to perform smMIP-based enrichment and sequencing for BRCA1, BRCA2, and the checkpoint kinase 2 (CHEK2) c.1100del variant. RESULTS Pathogenic and benign variants were analyzed in a subset of 152 previously BRCA-genotyped samples, yielding an analytical sensitivity and specificity of 100%. Following automation, blind analysis of 65 in-house samples and 267 Norwegian samples correctly identified all true-positive variants (>3000), with no false positives. Consequent to process optimization, turnaround times were reduced by 60% to currently 10–15 days. Copy number variants were detected with an analytical sensitivity of 100% and an analytical specificity of 88%. CONCLUSIONS smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.

Genetic Linkage Between the Collagen VII (COL7A1) Gene and the Autosomal Dominant Form of Dystrophic Epidermolysis Bullosa in Two Dutch Kindreds

1992 ◽  
Vol 99 (5) ◽  
pp. 528-530 ◽  
Author(s):  
Nelleke A Gruis ◽  
Jan N Bouwes Bavinck ◽  
Peter M Steijlen ◽  
Jan G Van Der Schroeff ◽  
Arie Van Haeringen ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Genetic Linkage ◽  
Autosomal Dominant ◽  
Dominant Form ◽  
Dystrophic Epidermolysis Bullosa ◽  
Autosomal Dominant Form ◽  
Col7a1 Gene ◽  
Collagen Vii

10q23.31 microduplication encompassing PTEN decreases mTOR signalling activity and is associated with autosomal dominant primary microcephaly

2018 ◽  
Vol 56 (8) ◽  
pp. 543-547 ◽  
Author(s):  
Danyllo Oliveira ◽  
Gabriela Ferraz Leal ◽  
Andréa L Sertié ◽  
Luiz Carlos Caires Jr ◽  
Ernesto Goulart ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Autism Spectrum ◽  
Signalling Pathway ◽  
Variable Degree ◽  
Primary Microcephaly ◽  
Dominant Form ◽  
Gene And Protein Expression ◽  
Autosomal Dominant Form ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

BackgroundHereditary primary microcephaly (MCPH) is mainly characterised by decreased occipitofrontal circumference and variable degree of intellectual disability. MCPH with a dominant pattern of inheritance is a rare condition, so far causally linked to pathogenic variants in the ALFY, DPP6, KIF11 and DYRK1A genes.ObjectiveThis study aimed at identifying the causative variant of the autosomal dominant form of MCPH in a Brazilian family with three affected members.MethodsFollowing clinical evaluation of two sibs and their mother presenting with autosomal dominant MCPH, array comparative genome hybridisation was performed using genomic DNA from peripheral blood of the family members. Gene and protein expression studies were carried out in cultured skin fibroblasts.ResultsA 382 kb microduplication at 10q23.31 was detected, encompassing the entire PTEN, KLLN and ATAD1 genes. PTEN haploinsufficiency has been causally associated with macrocephaly and autism spectrum disorder and, therefore, was considered the most likely candidate gene to be involved in this autosomal dominant form of MCPH. In the patients’ fibroblasts, PTEN mRNA and protein were found to be overexpressed, and the phosphorylation patterns of upstream and downstream components of the mammalian target of rapamycin (mTOR) signalling pathway were dysregulated.ConclusionsTaken together, our results demonstrate that the identified submicroscopic 10q23.31 duplication in a family with MCPH leads to markedly increased expression of PTEN and reduced activity of the mTOR signalling pathway. These results suggest that the most probable pathomechanism underlying the microcephaly phenotype in this family involves downregulation of the mTOR pathway through overexpression of PTEN.

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