Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

Science ◽  
2002 ◽  
Vol 299 (5604) ◽  
pp. 256-259 ◽  
Author(s):  
V. Bonifati
Keyword(s):  
Early Onset ◽  
Autosomal Recessive

scholarly journals A Novel Homozygous In-Frame Deletion in Complement Factor 3 Underlies Early-Onset Autosomal Recessive Atypical Hemolytic Uremic Syndrome - Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Shirley Pollack ◽  
Israel Eisenstein ◽  
Adi Mory ◽  
Tamar Paperna ◽  
Ayala Ofir ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Exome Sequencing ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Critical Role ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complement Factor ◽  
Complement Components ◽  
Uremic Syndrome ◽  
Close Relatives

Background and ObjectivesAtypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. Hereditary aHUS due to C3 disruption is rare, usually caused by heterozygous activating mutations in the C3 gene, and transmitted as autosomal dominant traits. We studied the molecular basis of early-onset aHUS, associated with an unusual finding of a novel homozygous activating deletion in C3.Design, Setting, Participants, & MeasurementsA male neonate with eculizumab-responsive fulminant aHUS and C3 hypocomplementemia, and six of his healthy close relatives were investigated. Genetic analysis on genomic DNA was performed by exome sequencing of the patient, followed by targeted Sanger sequencing for variant detection in his close relatives. Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother.ResultsExome sequencing revealed a novel homozygous variant in exon 26 of C3 (c.3322_3333del, p.Ile1108_Lys1111del), within the highly conserved thioester-containing domain (TED), fully segregating with the familial disease phenotype, as compatible with autosomal recessive inheritance. Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack complex, while his healthy heterozygous mother showed intermediate levels of C3 consumption.ConclusionsOur findings represent the first description of aHUS secondary to a novel homozygous deletion in C3 with ensuing unbalanced C3 over-activation, highlighting a critical role for the disrupted C3-TED domain in the disease mechanism.

scholarly journals Leptin receptor deficiency: a systematic literature review and prevalence estimation based on population genetics

2020 ◽  
Vol 182 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Lotte Kleinendorst ◽  
Ozair Abawi ◽  
Hetty J van der Kamp ◽  
Mariëlle Alders ◽  
Hanne E J Meijers-Heijboer ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Leptin Receptor ◽  
Pituitary Hormone ◽  
Sequencing Data ◽  
Prevalence Estimation ◽  
Calculation Results ◽  
Number Of Individuals

Objective Leptin receptor (LepR) deficiency is an autosomal-recessive endocrine disorder causing early-onset severe obesity, hyperphagia and pituitary hormone deficiencies. As effective pharmacological treatment has recently been developed, diagnosing LepR deficiency is urgent. However, recognition is challenging and prevalence is unknown. We aim to elucidate the clinical spectrum and to estimate the prevalence of LepR deficiency in Europe. Design Comprehensive epidemiologic analysis and systematic literature review. Methods We curated a list of LEPR variants described in patients and elaborately evaluated their phenotypes. Subsequently, we extracted allele frequencies from the Genome Aggregation Database (gnomAD), consisting of sequencing data of 77 165 European individuals. We then calculated the number of individuals with biallelic disease-causing LEPR variants. Results Worldwide, 86 patients with LepR deficiency are published. We add two new patients, bringing the total of published patients to 88, of which 21 are European. All patients had early-onset obesity; 96% had hyperphagia; 34% had one or more pituitary hormone deficiencies. Our calculation results in 998 predicted patients in Europe, corresponding to a prevalence of 1.34 per 1 million people (95% CI: 0.95–1.72). Conclusions This study shows that LepR deficiency is more prevalent in Europe (n = 998 predicted patients) than currently known (n = 21 patients), suggesting that LepR deficiency is underdiagnosed. An important cause for this could be lack of access to genetic testing. Another possible explanation is insufficient recognition, as only one-third of patients has pituitary hormone deficiencies. With novel highly effective treatment emerging, diagnosing LepR deficiency is more important than ever.

scholarly journals DEVELOPMENTAL DELAY IN CHILDHOOD CATARACT: A CAVEAT MARINESCO-SJÖGREN SYNDROME

2014 ◽  
Vol 04 (03) ◽  
pp. 121-123
Author(s):  
Rathika D. Shenoy ◽  
Deepthi R. V. ◽  
Nutan Kamath ◽  
Sumana J. Kamath
Keyword(s):  
Developmental Delay ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Cerebellar Hypoplasia ◽  
Psychomotor Delay ◽  
Neuro Imaging ◽  
Childhood Cataract

AbstractWe report on a child with Marinesco-Sjögren Syndrome, a rare autosomal recessive disorder characterised by early onset cataract, psychomotor delay, cerebellar hypoplasia and myopathy. The presentation, neuro-imaging and muscle biopsy features are discussed.

Early onset, autosomal recessive muscular dystrophy with Emergy-Dreifuss phenotype and normal emerin expression

Neurology ◽  
1998 ◽  
Vol 51 (4) ◽  
pp. 1116-1120 ◽  
Author(s):  
J. Taylor ◽  
C. A. Sewry ◽  
V. Dubowitz ◽  
F. Muntoni
Keyword(s):  
Muscular Dystrophy ◽  
Early Onset ◽  
Autosomal Recessive

Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila

Genome ◽  
2017 ◽  
Vol 60 (3) ◽  
pp. 241-247
Author(s):  
P. Githure M’Angale ◽  
Brian E. Staveley
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Control Mechanism ◽  
Nigrostriatal Neurons ◽  
Climbing Ability ◽  
Quality Control Mechanism ◽  
Locomotor Ability ◽  
Early Onset Parkinson’S Disease

Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson’s disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD. To further evaluate the effects of the overexpression of the Bcl-2 homologue Buffy, we analysed lifespan and climbing ability in both parkin-RNAi- and Pink1-RNAi-expressing flies. In addition, the effect of Buffy overexpression upon parkin-induced developmental eye defects was examined through GMR-Gal4-dependent expression. Curiously, Buffy overexpression produced very different effects: the parkin-induced phenotypes were enhanced, whereas the Pink1-enhanced phenotypes were suppressed. Interestingly, the overexpression of Buffy along with the inhibition of parkin in the neuron-rich eye results in the suppression of the developmental eye defects.

Two cases of early-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay diagnosed in adulthood

2021 ◽  
Vol 201 ◽  
pp. 106423
Author(s):  
Turgut Sahin ◽  
Fatma Tugra Karaarslan ◽  
Rezzak Yilmaz ◽  
Şeyma Tekgül ◽  
Ayşe Nazlı Başak ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
Spastic Ataxia

De novo variants in SLC12A6 cause sporadic early-onset progressive sensorimotor neuropathy

2019 ◽  
Vol 57 (4) ◽  
pp. 283-288 ◽  
Author(s):  
Joohyun Park ◽  
Bianca R Flores ◽  
Katalin Scherer ◽  
Hanna Kuepper ◽  
Mari Rossi ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
De Novo ◽  
Brain Mri ◽  
Sensory Neuropathy ◽  
Sensorimotor Neuropathy ◽  
Charcot Marie Tooth Disease ◽  
Functional Characterisation ◽  
Potassium Influx ◽  
Tooth Disease

BackgroundCharcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system. Biallelic variants in SLC12A6 have been associated with autosomal-recessive hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC). We identified heterozygous de novo variants in SLC12A6 in three unrelated patients with intermediate CMT.MethodsWe evaluated the clinical reports and electrophysiological data of three patients carrying de novo variants in SLC12A6 identified by diagnostic trio exome sequencing. For functional characterisation of the identified variants, potassium influx of mutated KCC3 cotransporters was measured in Xenopus oocytes.ResultsWe identified two different de novo missense changes (p.Arg207His and p.Tyr679Cys) in SLC12A6 in three unrelated individuals with early-onset progressive CMT. All presented with axonal/demyelinating sensorimotor neuropathy accompanied by spasticity in one patient. Cognition and brain MRI were normal. Modelling of the mutant KCC3 cotransporter in Xenopus oocytes showed a significant reduction in potassium influx for both changes.ConclusionOur findings expand the genotypic and phenotypic spectrum associated with SLC12A6 variants from autosomal-recessive HMSN/ACC to dominant-acting de novo variants causing a milder clinical presentation with early-onset neuropathy.

Identification of an RP1 Prevalent Founder Mutation and Related Phenotype in Spanish Patients with Early-Onset Autosomal Recessive Retinitis

Ophthalmology ◽  
2012 ◽  
Vol 119 (12) ◽  
pp. 2616-2621 ◽  
Author(s):  
Almudena Avila-Fernandez ◽  
Marta Corton ◽  
Koji M. Nishiguchi ◽  
Nelida Muñoz-Sanz ◽  
Belen Benavides-Mori ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
Founder Mutation ◽  
Related Phenotype

scholarly journals Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion

2014 ◽  
Vol 17 (4) ◽  
pp. 291-299 ◽  
Author(s):  
Kristof Van Schil ◽  
Françoise Meire ◽  
Marcus Karlstetter ◽  
Miriam Bauwens ◽  
Hannah Verdin ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Retinal Dystrophy ◽  
Autosomal Recessive Cerebellar Ataxia
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