Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical Genetics of Prolidase Deficiency: An Updated Review.

ABSTRACT: Prolidase is a ubiquitous enzyme that plays a major role in the metabolism of proline-rich proteins. Prolidase deficiency is a rare autosomal recessive inborn metabolic and multisystemic disease, characterized by a protean association of symptoms, namely intellectual disability, recurrent infections, splenomegaly, skin lesions, auto-immune disorders and cytopenia. To our knowledge, no published review has assembled the different clinical data and research studies over prolidase deficiency. The aim of this study is to summarize the actual state of the art from the descriptions of all the patients with a molecular diagnosis of prolidase deficiency reported to date regarding the clinical, biological, histopathological features, therapeutic options and functional studies.

SUBMITTER: Spodenkiewicz M

PROVIDER: S-EPMC7285180 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Clinical Genetics of Prolidase Deficiency: An Updated Review.

Spodenkiewicz Marta M Spodenkiewicz Michel M Cleary Maureen M Massier Marie M Fitsialos Giorgos G Cottin Vincent V Jouret Guillaume G Poirsier Céline C Doco-Fenzy Martine M Lèbre Anne-Sophie AS

Biology 20200521 5

Prolidase is a ubiquitous enzyme that plays a major role in the metabolism of proline-rich proteins. Prolidase deficiency is a rare autosomal recessive inborn metabolic and multisystemic disease, characterized by a protean association of symptoms, namely intellectual disability, recurrent infections, splenomegaly, skin lesions, auto-immune disorders and cytopenia. To our knowledge, no published review has assembled the different clinical data and research studies over prolidase deficiency. The a ...[more]

PMID: 32455636

Similar Datasets

Clinical Genetics of Polydactyly: An Updated Review.

Project description:Polydactyly, also known as hyperdactyly or hexadactyly is the most common hereditary limb anomaly characterized by extra fingers or toes, with various associated morphologic phenotypes as part of a syndrome (syndromic polydactyly) or may occur as a separate event (non-syndromic polydactyly). Broadly, the non-syndromic polydactyly has been classified into three types, i.e.; preaxial polydactyly (radial), central polydactyly (axial), and postaxial polydactyly (ulnar). Mostly inherited as an autosomal dominant entity with variable penetrance and caused by defects that occur in the anterior-posterior patterning of limb development. In humans, to-date at least 10 loci and six genes causing non-syndromic polydactyly have been identified, including the ZNF141, GLI3, MIPOL1, IQCE, PITX1, and the GLI1. In the present review, clinical, genetic and molecular characterization of the polydactyly types has been presented including the recent genes and loci identified for non-syndromic polydactyly. This review provides an overview of the complex genetic mechanism underlie polydactyly and might help in genetic counseling and quick molecular diagnosis.

| S-EPMC6232527 | biostudies-literature

Four novel PEPD alleles causing prolidase deficiency.

Project description:Mutations at the PEPD locus cause prolidase deficiency (McKusick 170100), a rare autosomal recessive disorder characterized by iminodipeptiduria, skin ulcers, mental retardation, and recurrent infections. Four PEPD mutations from five severely affected individuals were characterized by analysis of reverse-transcribed, PCR-amplified (RT-PCR) cDNA. We used SSCP analysis on four overlapping cDNA fragments covering the entire coding region of the PEPD gene and detected abnormal SSCP bands for the fragment spanning all or part of exons 13-15 in three of the probands. Direct sequencing of the mutant cDNAs showed a G-->A, 1342 substitution (G448R) in two patients and a 3-bp deletion (delta E452 or delta E453) in another. In the other two probands the amplified products were of reduced size. Direct sequencing of these mutant cDNAs revealed a deletion of exon 5 in one patient and of exon 7 in the other. Intronic sequences flanking exons 5 and 7 were identified using inverse PCR followed by direct sequencing. Conventional PCR and direct sequencing then established the intron-exon borders of the mutant genomic DNA revealing two splice acceptor mutations: a G-->C substitution at position -1 of intron 4 and an A-->G substitution at position -2 of intron 6. Our results indicate that the severe form of prolidase deficiency is caused by multiple PEPD alleles. In this report we attempt to begin the process of describing these alleles and cataloging their phenotypic expression.

| S-EPMC1918181 | biostudies-literature

Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review.

Project description:INTRODUCTION: Prolidase deficiency (PD) is a rare autosomal recessive disorder which may have a wide spectrum of clinical features. These features include a characteristic facies, cognitive impairment, rashes or skin ulceration, splenomegaly, recurrent infections involving mainly the respiratory system, and iminodipeptiduria. The disorder is caused by a mutation in the PEPD gene. OBJECTIVE: To describe a cohort of unrelated PD patients from Northern Israel whose inborn error of metabolism was associated with systemic lupus erythematosus (SLE) and to identify in the medical literature all PD cases mimicked by and/or associated with SLE. METHODS: Three patients with PD associated with SLE were clinically, biochemically and genetically investigated. These patients were from 3 unrelated consanguineous families residing in Northern Israel. A computer-assisted (PubMed) search of the medical literature from 1975 to 2011 was performed using the following key words: Prolidase deficiency, SLE, and systemic lupus erythematosus. RESULTS: An association between PD and SLE was found in 10 PD patients. These 10 patients included three from our cohort of 23 PD patients, and seven out of just under 70 PD patients previously reported in the literature. CONCLUSION: The present findings underscore the relatively high incidence of the association between SLE and PD, suggesting that this association may not be coincidental. The phenotypic similarities between SLE and PD might suggest that the PEPD gene constitutes a modifier gene or a genetic risk factor in the causation of SLE.

| S-EPMC3623899 | biostudies-literature

Prolidase deficiency breaks tolerance to lupus-associated antigens.

Project description:AIM:Prolidase deficiency is a rare autosomal recessive disease in which one of the last steps of collagen metabolism, cleavage of proline-containing dipeptides, is impaired. Only about 93 patients have been reported with about 10% also having systemic lupus erythematosus (SLE). METHODS:We studied a large extended Amish pedigree with four prolidase deficiency patients and three heterozygous individuals for lupus-associated autoimmunity. Eight unaffected Amish children served as normal controls. Prolidase genetics and enzyme activity were confirmed. Antinuclear antibodies (ANA) were determined using indirect immunofluorescence and antibodies against extractable nuclear antigens were determined by various methods, including double immunodiffusion, immunoprecipitation and multiplex bead assay. Serum C1q levels were determined by enzyme-linked immunosorbent assay. RESULTS:Two of the four homozygous prolidase deficiency subjects had a positive ANA. One had anti-double-stranded DNA, while another had precipitating anti-Ro. By the simultaneous microbead assay, three of the four had anti-Sm and anti-chromatin. One of the three heterozygous subjects had a positive ANA and immunoprecipitation of a 75 000 molecular weight protein. The unaffected controls had normal prolidase activity and were negative for autoantibodies. CONCLUSIONS:Prolidase deficiency may be associated with the loss of immune tolerance to lupus-associated autoantigens even without clinical SLE.

| S-EPMC4030668 | biostudies-literature

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review.

Project description:BACKGROUND:Atopic dermatitis is a common inflammatory skin disorder that affects up to 15-20% of the population and is characterized by recurrent eczematous lesions with intense itching. As a heterogeneous disease, multiple factors have been suggested to explain the nature of atopic dermatitis (AD), and its high prevalence makes it necessary to periodically compile and update the new information available. In this systematic review, the focus is set at the genetic and epigenetic studies carried out in the last years. METHODS:A systematic literature review was conducted in three scientific publication databases (PubMed, Cochrane Library, and Scopus). The search was restricted to publications indexed from July 2016 to December 2019, and keywords related to atopic dermatitis genetics and epigenetics were used. RESULTS:A total of 73 original papers met the inclusion criteria established, including 9 epigenetic studies. A total of 62 genes and 5 intergenic regions were described as associated with AD. CONCLUSION:Filaggrin (FLG) polymorphisms are confirmed as key genetic determinants for AD development, but also epigenetic regulation and other genes with functions mainly related to the immune system and extracellular matrix, reinforcing the notion of skin homeostasis breakage in AD.

| S-EPMC7231115 | biostudies-literature

Genetics of adult attachment: An updated review of the literature.

Project description:Attachment style, which has been theorized to be rooted in childhood bonding experiences, influences adult cognitive, emotional and interpersonal functioning. Despite its relationship with early experiences, research indicates that the continuity of attachment style across childhood and adulthood is only partial, being a malleable tendency that is shaped throughout development, with an increasing influence of genetics, as it occurs in other cognitive and behavioral phenotypes. Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes, but the precise mechanisms remain unclear. A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin, dopaminergic pathways, serotonergic pathways and brain-derived neurotrophic factor in adult attachment, with both vulnerability and differential susceptibility approaches, yielding mixed results. We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation. Based on the existing data, we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.

| S-EPMC8474999 | biostudies-literature

Expression and molecular analysis of mutations in prolidase deficiency.

Project description:Prolidase (E.C.3.4.13.9) cleaves iminodipeptides. Prolidase deficiency (PD; McKusick 170100) is an autosomal recessive disorder with highly variable penetrance. We have identified two novel alleles in the prolidase gene (PEPD) by direct sequencing of PCR-amplified cDNA from a PD individual asymptomatic at age 11 years: a 551G-->A transition in exon 8 (R184Q) and a 833G-->A transition in exon 12 (G278D). To assess the biochemical phenotypes of these and two previously identified PEPD mutations (G448R and delE452), we have designed a transient-expression system for prolidase in COS-1 cells. The enzyme was expressed as a fusion protein carrying an N-terminal tag, the HA1 epitope of influenza hemagglutinin, allowing its immunological discrimination from the endogenous enzyme with a monoclonal antibody. Expression of the R184Q mutation produced 7.4% of control enzymatic activity whereas the expression of the G278D, G448R, and delE452 mutations produced inactive enzymes. Western analysis of the R184Q, G278D, and G448R prolidases revealed stable immunoreactive material whereas the delE452 prolidase was not detectable. Pulse-chase metabolic labeling of cells followed by immunoprecipitation revealed that the delE452 mutant protein was synthesized but had an increased rate of degradation.

| S-EPMC1914827 | biostudies-literature

An Updated Review on the Genetics of Primary Open Angle Glaucoma.

Project description:Epidemiological studies suggest that by 2020 the prevalence of primary open angle glaucoma (POAG) is estimated to increase to 76.0 million, and to 111.8 million by 2040 globally due to the population aging. The prevalence of POAG is the highest among those of African descent, followed by Asians, and the lowest in Europeans. POAG is a genetically complex trait with a substantial fraction exhibiting a significant heritability. Less than 10% of POAG cases in the general population are caused by specific gene mutations and the remaining cases are polygenic. Quantitative traits related to POAG pathogenesis such as intra-ocular pressure (IOP), vertical cup/disc ratio (VCDR), optic disc area, and central corneal thickness (CCT) are highly heritable, and likely to be influenced at least in part by genes and show substantial variation in human populations. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) at different loci including CAV1/CAV2, TMCO1, CDKN2B-AS1, CDC7-TGFBR3, SIX1/SIX6, GAS7 and ATOH7 to be associated with POAG and its related quantitative traits (endophenotypes). The chapter provides a brief overview on the different GWAS and SNP association studies and their correlation with various clinical parameters important for POAG in the population worldwide, including the Middle East.

| S-EPMC4691082 | biostudies-literature

Sucrosomial<sup>®</sup> Iron: An Updated Review of Its Clinical Efficacy for the Treatment of Iron Deficiency.

Project description:Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent worldwide. Oral iron salts, especially ferrous sulfate, are commonly used for the treatment of iron deficiency (ID). However, its use is associated with gastrointestinal side effects, thus compromising treatment compliance. Intravenous iron administration is a more costly and logistically complex alternative and is not risk-free, as infusion and hypersensitivity reactions may occur. Sucrosomial® iron is an oral formulation consisting of ferric pyrophosphate conveyed by a phospholipid and sucrester matrix (sucrosome®). Intestinal Sucrosomial® iron absorption is mediated by enterocytes and M cells, through the paracellular and transcellular routes, and occurs mostly as intact particles. These pharmacokinetic properties of Sucrosomial® iron result in higher iron intestinal absorption and excellent gastrointestinal tolerance compared to oral iron salts. The evidence derived from clinical studies supports the use of Sucrosomial® iron as a valid first option for the treatment of ID and IDA, especially for subjects who are intolerant or refractory to conventional iron salts. Newer evidence also demonstrates the effectiveness of Sucrosomial® iron, with a lower cost and fewer side effects, in certain conditions usually treated with IV iron in current clinical practice.

| S-EPMC10305423 | biostudies-literature

Chronic Liver Disease in Patients with Prolidase Deficiency: A Case Series.

Project description:IntroductionProlidase deficiency is a rare autosomal recessive disorder caused by variants in the PEPD gene. Patients usually have multi-organ involvement and a wide range of clinical features including recurrent skin ulcers, dysmorphic facial features, recurrent infections, intellectual disability, and splenomegaly. Studies have shown that patients with prolidase deficiency may have hepatic manifestations including hepatomegaly and abnormal liver enzymes. However, there is no detailed description of liver disease in this patient population.Case presentationHere, we present 3 patients with prolidase deficiency with varying extents of hepatic involvement.ConclusionProlidase deficiency patients with liver disease should be followed up long term to understand more about the pathophysiology and the impact of liver disease on long-term outcomes.

| S-EPMC10834036 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data