Fumarase Deficiency in Dichorionic Diamniotic Twins

2013 ◽  
Vol 16 (6) ◽  
pp. 1117-1120 ◽  
Author(s):  
Simone Tregoning ◽  
Wendy Salter ◽  
David R. Thorburn ◽  
Miranda Durkie ◽  
Maria Panayi ◽  
...  
Keyword(s):  
Disease Burden ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Tricarboxylic Acid Cycle ◽  
Fumarate Hydratase ◽  
Global Developmental Delay ◽  
Hepatic Involvement ◽  
Increased Risk ◽  
Heterozygous Carriers ◽  
Fumarase Deficiency

Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.

A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency

2004 ◽  
Vol 82 (8) ◽  
Author(s):  
AnneM. Remes ◽  
SirpaA. Filppula ◽  
Heikki Rantala ◽  
Jaakko Leisti ◽  
Aimo Ruokonen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Fumarase Deficiency

scholarly journals Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice

2021 ◽  
Author(s):  
Suzanne C. E. H. Sallevelt ◽  
Alexander P. A. Stegmann ◽  
Bart de Koning ◽  
Crool Velter ◽  
Anja Steyls ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Rare Variants ◽  
Clinical Care ◽  
Carrier Testing ◽  
Carrier Status ◽  
Routine Diagnostics ◽  
Affected Offspring ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Genetics And Genomics

Abstract Purpose Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care. Methods We performed exome sequencing (ES) for 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic variants in offspring were selected. These variants were subsequently filtered against a gene panel consisting of ~2,000 genes associated with known AR disorders (OMIM-based). Remaining variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic and pathogenic (class IV/V) variants, present in both partners, were reported. Results In 28 of 100 tested consanguineous couples (28%), likely pathogenic and pathogenic variants not previously known in the couple or their family were reported conferring 25% risk of affected offspring. Conclusion ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples. Outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.

scholarly journals Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samina Yasin ◽  
Outi Makitie ◽  
Sadaf Naz
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Loss Of Function ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Skeletal Malformations ◽  
Tarsal Bones ◽  
The Family ◽  
Heterozygous Carriers

Abstract Background Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. Case presentation We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. Conclusion Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

scholarly journals Risk of sexually transmitted Zika virus in a cohort of economically disadvantaged urban residents

2021 ◽  
Author(s):  
Juan P Aguilar Ticona ◽  
Huma Baig ◽  
Nivison Nery Jr. ◽  
Simon Doss-Gollin ◽  
Gielson A Sacramento ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Sexually Transmitted Infections ◽  
Zika Virus ◽  
Disease Burden ◽  
Urban Community ◽  
Urban Residents ◽  
Zikv Infection ◽  
Retrospective Survey ◽  
Sexually Transmitted ◽  
Increased Risk

Abstract In order to understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil through the 2015 ZIKV epidemic. Later, in 2017, we used a retrospective survey to associate sexual behavior during the epidemic with ZIKV infection as defined by IgG3-NS1 ELISA. We found that males who engaged in casual sexual encounters during the epidemic were more likely (ORa=6.2; 95%CI 1.2–64.1) to be ZIKV positive, suggesting that specific groups may be at increased risk of sexually transmitted infections.

scholarly journals Examination of the predicted prevalence of Gitelman syndrome by ethnicity based on genome databases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Kondo ◽  
China Nagano ◽  
Shinya Ishiko ◽  
Takashi Omori ◽  
Yuya Aoto ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Carrier Frequency ◽  
Japanese Population ◽  
Autosomal Recessive ◽  
Disease Prevalence ◽  
Gitelman Syndrome ◽  
Variant Allele ◽  
Variant Allele Frequency ◽  
Genome Databases ◽  
Heterozygous Carriers

AbstractGitelman syndrome is an autosomal recessive inherited salt-losing tubulopathy. It has a prevalence of around 1 in 40,000 people, and heterozygous carriers are estimated at approximately 1%, although the exact prevalence is unknown. We estimated the predicted prevalence of Gitelman syndrome based on multiple genome databases, HGVD and jMorp for the Japanese population and gnomAD for other ethnicities, and included all 274 pathogenic missense or nonsense variants registered in HGMD Professional. The frequencies of all these alleles were summed to calculate the total variant allele frequency in SLC12A3. The carrier frequency and the disease prevalence were assumed to be twice and the square of the total allele frequency, respectively, according to the Hardy–Weinberg principle. In the Japanese population, the total carrier frequencies were 0.0948 (9.5%) and 0.0868 (8.7%) and the calculated prevalence was 0.00225 (2.3 in 1000 people) and 0.00188 (1.9 in 1000 people) in HGVD and jMorp, respectively. Other ethnicities showed a prevalence varying from 0.000012 to 0.00083. These findings indicate that the prevalence of Gitelman syndrome in the Japanese population is higher than expected and that some other ethnicities also have a higher prevalence than has previously been considered.

A Targeted Literature Review of the Disease Burden in Patients With Symptomatic Peripheral Artery Disease

Angiology ◽  
2019 ◽  
Vol 71 (4) ◽  
pp. 303-314
Author(s):  
Rupert Bauersachs ◽  
Sebastian Debus ◽  
Mark Nehler ◽  
Maria Huelsebeck ◽  
Janita Balradj ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Disease Burden ◽  
Ankle Brachial Index ◽  
Peripheral Artery ◽  
Economic Burden Of Disease ◽  
Surgical Interventions ◽  
Treatment Practice ◽  
Patient Profile ◽  
Increased Risk ◽  
Artery Disease

Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle–brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.

Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 692-694 ◽  
Author(s):  
Daniel F. Wallace ◽  
Palle Pedersen ◽  
Jeannette L. Dixon ◽  
Peter Stephenson ◽  
Jeffrey W. Searle ◽  
...  
Keyword(s):  
Iron Transport ◽  
Autosomal Recessive ◽  
Iron Homeostasis ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Hfe Gene ◽  
Excess Iron ◽  
Chromosome 1Q ◽  
Australian Family ◽  
Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

Heterozygous carriers of the I171V mutation of the NBS1 gene have a significantly increased risk of solid malignant tumours

2008 ◽  
Vol 44 (4) ◽  
pp. 627-630 ◽  
Author(s):  
Jerzy Nowak ◽  
Maria Mosor ◽  
Iwona Ziółkowska ◽  
Malgorzta Wierzbicka ◽  
Monika Pernak-Schwarz ◽  
...  
Keyword(s):  
Malignant Tumours ◽  
Nbs1 Gene ◽  
Increased Risk ◽  
Heterozygous Carriers ◽  
I171v Mutation

A novel mutation in thePLCD1gene, which leads to an aberrant splicing event, underlies autosomal recessive leuconychia

2012 ◽  
Vol 167 (4) ◽  
pp. 946-949 ◽  
Author(s):  
M. Farooq ◽  
M. Kurban ◽  
O. Abbas ◽  
O. Obeidat ◽  
H. Fujikawa ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Aberrant Splicing
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