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PubMed2026

A novel FLNA p.Pro2469Ser variant is associated with impaired T and NK cell function and immune dysregulation.

FLNA encodes filamin A, a ubiquitously expressed actin-binding cytoskeletal protein that cross-links actin filaments and links them to membrane-associated signaling complexes. Although FLNA has been implicated in T-cell signaling and regulatory T-cell development in murine models, its role in human immune-cell function remains incompletely understood. Here, we investigated the immunological phenotype associated with a novel hemizygous FLNA variant identified in a pediatric patient presenting with recurrent infections and inflammatory manifestations. Whole-exome sequencing revealed a hemizygous c.7405C>T (p.Pro2469Ser) variant in FLNA, which was confirmed by Sanger sequencing. Its potential impact on immune-cell function and cytoskeletal organization was evaluated using confocal microscopy, flow cytometry, and molecular assays. Patient-derived T cells showed impaired activation and proliferation following CD3/CD28 and IL-2 stimulation, accompanied by reduced CD25 and CD69 upregulation. CD4+ T cells also exhibited reduced IFN-γ, TNF-α, and IL-2 production after stimulation. Despite elevated basal phospho-STAT5 levels, IL-2-induced STAT5 phosphorylation and TCR-associated signaling responses, including pZAP70, pLCK, and p38 MAPK activation, were attenuated. Confocal imaging together with image-based quantification demonstrated altered cortical cytoskeletal organization in patient T cells despite preserved FLNA expression. In parallel, NK cells showed impaired activation responses and reduced cytotoxic activity under the assay conditions used. Increased apoptosis was observed in CD4⁺, CD8⁺, and NK-cell populations. Inflammatory cytokines were elevated in plasma and colonic tissue, whereas colonic ZO-1 and FLNA expression were reduced. Collectively, these findings indicate that the FLNA p.Pro2469Ser variant is associated with altered immune-cell signaling, disturbed cortical cytoskeletal organization, and immune dysregulation. This study expands the phenotypic spectrum linked to FLNA variants and supports a role for filamin A in human immune-cell regulation.

Humans↗

PubMed2025

AUTS2-related syndrome: Insights from a large European cohort.

PURPOSE: AUTS2-related syndrome is characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters, AUTS2 encodes 2 distinct long and short isoforms encoding a putative transcriptional activator. METHODS: Through a European collaborative study, we collected clinical and genotype data on the largest AUTS2-related syndrome cohort of 58 patients harboring genomic rearrangements or single-nucleotide variants (SNVs). RESULTS: Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent of the underlying defect at the AUTS2 locus, we observed that autistic behavior, hyperactivity, learning difficulties, and speech delay are common features of AUTS2-related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both longer and shorter AUTS2 transcripts showed a recognizable phenotype with microcephaly, brachycephaly, microretrognathia, broad nasal base, and anteverted nares. Behavioral disorders were more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only observed in patients with SNVs. CONCLUSION: This study provides a comprehensive clinical characterization of AUTS2-related syndrome, reveals few genotype-phenotype correlations, and suggests that the disruption of the 2 distinct AUTS2 transcripts has a different impact on the clinical phenotype.

Humans↗

PubMed1999

Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

Adolescent↗

PubMed1985

[Malignant fibrous histiocytoma of the soft tissues].

Clinico-morphological characterization of the malignant fibrous histiocytoma (MFH) of soft tissues in 142 patients is presented. According to the authors' data MFH is the most frequent tumour among soft tissue malignant neoplasms (15,7%) in adult patients. The age of patients is predominantly from 40 to 70, the most frequent site is a lower limb (thigh). A typical morphological variant of MFH clearly dominates (73%): there is a tendency to the development of an inflammatory variant at the retroperitoneal tumour site. Recurrences in all group of patients (104) who were followed-up were in 68,3%, metastasis in 45,2%, the 5-year survival in 59,6% of cases. A clear-cut dependence of these indices upon the depth of tumour location soft tissues, node size, tumour site is noted. In view of pronounced domination of a MFH typical variant the final conclusion on the feasibility of separation of other variants can be only made on the basis of a much greater number of cases.

Adolescent↗

PubMed1989

Total facial nerve decompression for recurrent facial paralysis: an update.

Recurrent facial paralysis (RFP) is a rare disorder that in some individuals may lead to worsening sequelae. Melkersson-Rosenthal syndrome is a variant of RFP that is associated with recurrent facial edema. In the past, decompression of the mastoid segment of the facial nerve has not been successful in preventing recurrences. In 1981 we began performing total facial nerve decompression for RFP and in 1986 reported its efficacy in one patient with Melkersson-Rosenthal syndrome and in another in whom both nerves were decompressed for alternating bilateral paralysis. An additional four cases with 3 to 8 years of followup demonstrate no recurrences in any patient. Total facial nerve decompression for RFP in selected patients appears efficacious in preventing recurrences. Decompression will remain investigational until further followup is obtained. Furthermore, its salutary effect should not be extrapolated to Bell's palsy without further study.

Adolescent↗

PubMed1999

A heterozygous mutation of beta-actin associated with neutrophil dysfunction and recurrent infection.

A human disorder caused by mutation in nonmuscle actin has not been reported. We report here a variant of nonmuscle actin in a female patient with recurrent infections, photosensitivity, and mental retardation. She also had abnormalities in neutrophil chemotaxis, superoxide production, and membrane potential response. Two-dimensional PAGE analysis of proteins from neutrophils and other cell types from this patient demonstrated a unique protein spot migrating at 42 kDa with pI shifted slightly to neutral relative to normal beta- and gamma-actin. Digestion peptide mapping and Western blotting showed this spot to be an abnormal actin. A full-length cDNA library was constructed by using mRNA from patient's cells and cDNA encoding the mutant beta-actin molecule was identified by an in vitro translation method. Sequencing of the clones demonstrated a G-1174 to A substitution, predicting a glutamic acid-364 to lysine substitution in beta-actin and eliminating a HinfI DNase restriction site found in normal beta-actin sequence. By HinfI digestion and by sequencing, the mutation in one allele of patient's genomic DNA was confirmed. Though no defect in cell-free polymerization of actin was detected, this defect lies in a domain important for binding to profilin and other actin-regulatory molecules. In fact, the mutant actin bound to profilin less efficiently than normal actin did. Heterozygous expression of mutant beta-actin in neutrophils and other cells of this patient may act in a dominant-negative fashion to adversely affect cellular activities dependent on the function of nonmuscle actin.

Actins↗

PubMed2000

["Inner perilymph fistula" of the anterior semicircular canal. A new disease picture with recurrent attacks of vertigo].

In 1998 Minor et al. described a new variant of perilymphatic fistula: the "superior canal dehiscence syndrome". This syndrome is clinically characterized by recurrent attacks of vertigo and oscillopsia induced by loud noises or stimuli that result in changes in intracranial or middle ear pressure. It is caused by a dehiscence of bone overlying the superior (anterior) semicircular canal. Due to this dehiscence, a third, mobile window (in addition to the round and oval windows) is formed, and changes in pressure are pathologically transduced to the anterior semicircular canal. Although the superior canal dehiscence syndrome is not a rare condition, no other cases have yet been reported. Therefore, we describe a typical patient who suffered for many years from recurrent attacks of vertigo and oscillopsia induced by coughing and Valsalva's maneuvers. High resolution temporal bone CT scan showed a defect in the bone overlying the left anterior semicircular canal. Three-dimensional eye movement recordings using the search coil technique and subsequent vector analysis demonstrated that the eye movements were induced by excitation of the left anterior semicircular canal. We conclude that superior canal dehiscence syndrome is an important differential diagnosis in patients suffering from symptoms of a perilymphatic fistula, especially since it can be successfully treated by "plugging" of the affected semicircular canal. Such patients are thus spared unnecessary surgery of the middle ear.

Diagnosis, Differential↗

PubMed1986

[Recurrence tendency and malignant transformation of pleomorphic adenomas].

Young patients and those with the stroma-rich variant of pleomorphic adenoma have an increased risk of local recurrence. Review of 98 patients with recurrent pleomorphic adenoma showed that the primary operation is nevertheless decisive for the further progress of the disease: incomplete tumour excision and enucleation of pleomorphic adenomas were responsible for tumour recurrence which may be multiple. Recurrence in turn favours the development of carcinoma within pleomorphic adenomas. Of 23 carcinomas, 20 developed within recurrent tumours. These 20 tumours comprised 16.9% of all recurrences observed. A mean time of 16 years relapsed after the primary operation before a carcinoma developed in the recurrence. Slow and protracted tumour growth were characteristic of those carcinomas that could be also demonstrated in the original tumour (0.9% of the group of non-recurrent tumours) with a mean time of 7 years before operation. Immediate tumour removal is therefore the best prophylaxis against carcinoma. In 19 patients we showed that local recurrence due to dissemination can be avoided by appropriate measures, even after intra-operative opening of the tumour capsule.

Adenoma↗

PubMed1989

[The treatment of relapses of non-Hodgkin's lymphomas].

It was established that radiation treatment followed by 1-2 courses of polychemotherapy proved optimal in the management of the first recurrences of non-Hodgkin's lymphomas with a favourable course of the local character. It is concluded that in the treatment of the first recurrences of non-Hodgkin's lymphomas choice of the treatment tactics should depend on the cytomorphological variant of the primary tumour, character of the recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Staging of the pathophysiologic responses of the primate microvasculature to Escherichia coli and endotoxin: examination of the elements of the compensated response and their links to the corresponding uncompensated lethal variants.

OBJECTIVE: Review of primate studies of Escherichia coli sepsis and endotoxemia with a reexamination of the rationale for diagnosis and treatment of these multistage disorders. SETTING: Animal research and intensive care units in a university medical school. SUBJECTS: Cyanocephalus baboons (E. coli) and normal human subjects (endotoxin). INTERVENTIONS: Baboon studies: anti-tissue factor, protein C, endothelial protein C receptor, and anti-tumor necrosis factor antibodies, and active site inhibited factor recombinant VIIa and factor Xa. RESULTS AND CONCLUSIONS: This review concerns the primate microvascular endothelial response to inflammatory and hemostatic stress. Studies of the impact of inflammatory and hemostatic stress on this microvasculature have fallen into four categories. First, studies of pure hemostatic stress using factor Xa phospholipid vesicles showed that blockade of protein C as well as protein C plus tissue plasminogen activator produced a severe but transient consumptive and a lethal thrombotic coagulopathy, respectively. These studies showed that the protein C and fibrinolytic systems can work in tandem to regulate even a severe response if the endothelium is not rendered dysfunctional by metabolic or inflammatory factors. Second, studies of compensated (nonlethal) inflammatory stress using E. coli or endotoxin in baboon and human subjects showed that even under minimal stress in which there is no evidence of overt disseminated intravascular coagulation, injury of the endothelium and activation of neutrophils and hemostatic factors are closely associated. This showed that molecular markers of hemostatic activity could be used to detect microvascular endothelial stress (nonovert disseminated intravascular coagulation) in patients who are compensated but at risk. These studies also showed that the compensated response to inflammatory stress could exhibit two stages, each with its unique inflammatory and hemostatic response signature. The first is driven by vasoactive peptides, cytokines, and thrombin, followed 12 to 14 hrs later by a second stage driven by C-reactive protein/complement complexes, tissue factor, and plasminogen activator inhibitor 1 secondary to oxidative stress after reperfusion. Third, studies of uncompensated (lethal) inflammatory stress using E. coli showed that irreversible thrombosis of the microvasculature was not a link in the lethal chain of events even though inhibition of components of the protein C network (protein C and endothelial protein C receptor) converted compensated responses to sublethal E. coli into uncompensated lethal responses. Fourth, these studies also showed that there were variants of the lethal response ranging from capillary leak and shock to recurrent sustained inflammatory disorders. We believe that each of these variants arises from their sublethal counterparts, depending on underlying or modulating host factors operating at the time of challenge. Such underlying conditions range from preexisting microvascular ischemia, reperfusion, and oxidative stress to alteration or reprogramming of monocyte/macrophage responses (tolerance to hyperresponsiveness). Characterization of these underlying conditions in patients who are at risk should aid in identifying and optimizing management of these variants.

Animals↗

PubMed1981

[Structural variants, hyperplastic changes and tumors of the major duodenal papilla (based on surgical material from patients with chronic recurrent pancreatitis)].

Morphological studies of 15 polyps of the major duodenal papilla (MDP), 50 amputated MDPs and 5 ectomized MDPs from patients with chronic relapsing pancreatitis were carried out. Three groups of changes were detected: (1) variants of the structure: separate confluence of the common bile and major pancreatic ducts into the duodenum, additional pancreatic ducts, dystopia of the pancreatic gland tissue; (2) hyperplastic changes: papillomatosis of the MDP opening, intrapapillar adenomatous polyps, adenomyosis of MDP wall; (3) tumors: adenoma and carcinomas. No relationship between hyperplasias and calculi and inflammation of bile ducts was confirmed. Some kinds of MDP pathology were found to depend on variants of its structure. Papillomatosis of MDP was shown to be capable of malignancy.

Adolescent↗

PubMed2002

The contribution of genetic factors to thrombotic and bleeding outcomes in coronary patients randomised to IIb/IIIa antagonists.

Genetic variants are risk factors for coronary disease, but their role in recurrent events and in response to treatment is less clear. We genotyped genetic variants implicated in primary coronary disease in 924 Caucasians with acute coronary syndromes participating in the OPUS-TIMI16 trial of the GPIIb/IIIa antagonist orbofiban. These were the platelet glycoprotein (GP) receptors GPIIIa, GPIa, GPIbalpha; platelet ligands beta-fibrinogen and von Willebrand Factor (vWF); interleukins (IL) IL-1RN, and IL-6; adhesion proteins E-selectin and P-selectin; and metalloproteinase MMP-9. Cox modelling of all genetic variants demonstrated no significant impact on the composite endpoint (P = 0.88), which included myocardial infarction (MI), death, recurrent ischemia, urgent revascularisation and stroke, but a significant impact on recurrent myocardial infarction alone (chi(2) = 20.4, 10 df, P = 0.04). There was a significant interaction of the polymorphisms with orbofiban treatment influencing bleeding outcomes (P = 0.004). Thus, genetic polymorphisms may be associated with subsequent myocardial infarction, and may also be associated with treatment-associated bleeding among coronary patients.

Alanine↗

PubMed2002

Sphincter of Oddi (pancreatic) hypertension and recurrent pancreatitis.

Major papilla pancreatic sphincter dysfunction, a variant of sphincter of Oddi dysfunction, causes pancreatitis and pancreatic-type pain. The gold standard for diagnosis is sphincter of Oddi manometry, most commonly performed at endoscopic retrograde cholangiopancreatography (ERCP). Noninvasive testing, such as secretin-stimulated transabdominal or endoscopic ultrasound assessment of pancreatic duct diameter, is less reliable and has relatively low sensitivity. Two thirds of patients with biliary sphincter of Oddi dysfunction have elevated pancreatic basal sphincter pressure. To maximize the diagnostic yield of sphincter of Oddi dysfunction, both the biliary and pancreatic sphincter pressures should be measured. Patients with sphincter of Oddi dysfunction may respond to biliary sphincterotomy alone, but evaluation of their pancreatic sphincter is warranted if symptoms persist after biliary therapy alone. Whether both biliary and pancreatic sphincters should be treated at the first ERCP session is controversial. Biliary and pancreatic endoscopic sphincterotomies are associated with two- to fourfold increased incidence of pancreatitis following the procedure in patients with pancreatic sphincter hypertension. Prophylactic pancreatic duct stenting reduces the frequency and severity of complications by greater than 50%.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed2000

Surgical management of recurrent pancreatitis in children with pancreas divisum.

OBJECTIVE: To analyze an institutional experience with pancreatitis in childhood to clarify the frequency of pancreas divisum in that patient population, the characteristics of pancreatitis in children with pancreas divisum, and the role of surgical management in their treatment. SUMMARY BACKGROUND DATA: The role of pancreas divisum in causing acute and relapsing pancreatitis and chronic, recurring abdominal pain is controversial. Although the anatomical abnormality is present from birth, most investigators have reported cases with onset of symptoms in adulthood. The reported pediatric experience with this disorder is small, and the natural history of pancreatitis in children with pancreas divisum has not been well elucidated. METHODS: A retrospective chart review of all children 18 years of age and younger with a discharge diagnosis of pancreatitis identified 135 patients treated in the authors' institution from 1978 to 1998. Ten patients were found to have anatomical variants of pancreas divisum associated with recurrent or chronic pancreatitis. The medical records of these patients were reviewed for data on the presentation, diagnostic findings, imaging studies, treatment, surgical findings, and pathologic findings in these children. Chart review and telephone calls were used to assess the current state of health in nine patients available for follow-up. RESULTS: Pancreas divisum was identified in 7.4% of all children with pancreatitis and 19.2% of children with relapsing or chronic pancreatitis. Patients had early onset of recurrent episodic epigastric pain and vomiting, at a mean age of 6 years. Three patients had a positive family history of pancreatitis and one was proven by DNA analysis to have hereditary pancreatitis. Pancreatitis was documented by elevated amylase or lipase levels, and endoscopic retrograde cholangiopancreatography was the method of diagnosis of pancreas divisum in all patients. Eight patients had complete pancreas divisum and two had incomplete variants. Eight patients underwent surgery to improve ductal drainage. Seven underwent transduodenal sphincteroplasty of the accessory papilla, along with sphincteroplasty of the major papilla in two (plus septoplasty in one). Three patients underwent longitudinal pancreaticojejunostomy, as a primary procedure in one patient with midductal stenosis and in two because of recurring pancreatitis after sphincteroplasty. The surgical findings and histologic examination of five patients undergoing distal pancreatectomy revealed striking changes of advanced chronic pancreatitis. Patients responding to sphincteroplasty alone showed less severe histologic changes. Overall, three of seven patients had excellent results, three were improved, and one had continued disabling attacks of pancreatitis. The mean duration of follow-up was 7.3 years, and there were no deaths. No patients had endocrine or exocrine pancreatic insufficiency, and none required chronic analgesics. CONCLUSIONS: Pancreas divisum is an important cause of recurrent pancreatitis in childhood and should be sought aggressively in children with more than one episode of pancreatitis or pancreatitis with a history of chronic recurrent abdominal pain. Surgical intervention is directed toward relief of ductal obstruction and may involve accessory duct sphincteroplasty alone or in combination with major sphincteroplasty and septoplasty. Patients with more distal ductal obstruction or ductal ectasia may benefit from pancreaticojejunostomy.

Acute Disease↗

PubMed1985

Thornell's approach for arytenoidectomy in the surgical treatment of bilateral abductor paralysis; personal experience and results.

Surgical treatment of bilateral abductor paralysis of the vocal cords is still a question for debate, as can be seen by a review of the relevant literature. The authors describe their modification of Thornell's technique, as used in 12 cases of recurrent paralysis, and they suggest a variant to the basic method which has been proved to cause minimal trauma, is simple to carry out and has produced excellent results.

Adult↗

PubMed1993

IgG deficiency in adults with recurrent respiratory infections.

Total IgA, IgM, IgG, and IgG subclasses were measured in 136 consecutive adults with recurrent respiratory infections. Sinus and chest radiographs were also obtained. IgG antibodies to H. influenzae and tetanus toxoid were determined in 27 immunodeficient subjects. Fifty-eight of the 136 were deficient in some immunoglobulin isotype, three in IgA, three in IgM, and 52 in total IgG or one or more IgG subclasses. The most common IgG deficiencies were single IgG subclass deficiencies, particularly IgG3 or IgG4, and a mild decrease in total IgG (between 450 and 650 mg/dL). In 21/27 subjects with IgG deficiency, the response to booster immunization was blunted, even when IgG1 and IgG2 were normal. Thirty-eight patients were smokers, 37 being > 40 years of age at the onset of respiratory infections. Twenty patients were nonsmokers, 19 being < 40 years of age at the onset. In conclusion, adults with recurrent respiratory infections frequently have some variant of IgG deficiency, often associated with a functional impairment of specific antibody response. Smoking may represent a risk factor for IgG deficiency in adults.

Adult↗

PubMed2000

Diagnostic testing for Rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene: identification of several novel mutations and polymorphisms.

Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1/10,000-15,000 girls. The disease-causing gene was identified as MECP2 on chromosome Xq28, and mutations have been found in approximately 80% of patients diagnosed with RTT. Numerous mutations have been identified in de novo and rare familial cases, and they occur primarily in the methyl-CpG-binding and transcriptional-repression domains of MeCP2. Our first diagnostic strategy used bidirectional sequencing of the entire MECP2 coding region. Subsequently, we implemented a two-tiered strategy that used denaturing high-performance liquid chromatography (DHPLC) for initial screening of nucleotide variants, followed by confirmatory sequencing analysis. If a definite mutation was not identified, then the entire MECP2 coding region was sequenced, to reduce the risk of false negatives. Collectively, we tested 228 unrelated female patients with a diagnosis of possible (209) or classic (19) RTT and found MECP2 mutations in 83 (40%) of 209 and 16 (84%) of 19 of the patients, respectively. Thirty-two different mutations were identified (8 missense, 9 nonsense, 1 splice site, and 14 frameshifts), of which 12 are novel and 9 recurrent in unrelated patients. Seven unclassified variants and eight polymorphisms were detected in 228 probands. Interestingly, we found that T203M, previously reported as a missense mutation in an autistic patient, is actually a benign polymorphism, according to parental analysis performed in a second case identified in this study. These findings highlight the complexities of missense variant interpretation and emphasize the importance of parental DNA analysis for establishing an etiologic relation between a possible mutation and disease. Overall, we found a 98.8% concordance rate between DHPLC and sequence analyses. One mutation initially missed by the DHPLC screening was identified by sequencing. Modified conditions subsequently enabled its detection, underscoring the need for multiple optimized conditions for DHPLC analysis. We conclude that this two-tiered approach provides a sensitive, robust, and efficient strategy for RTT molecular diagnosis.

Alleles↗

PubMed2000

Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss.

An imbalance between phase I drug metabolizing enzymes and phase II detoxification enzymes may contribute to the development of pre-eclampsia. Polymorphic variants in the phase I enzyme, cytochrome P450 genes may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes may result in impaired detoxification. Most abundant in placenta and decidua is glutathione S-transferase P1-1, which may therefore be of particular importance in reproduction. We studied the frequencies of polymorphic variants in those enzymes in 187 women with recurrent early pregnancy loss and in 109 women with an uncomplicated obstetric history. DNA was extracted and subsequently polymerase chain reaction based genotyping assays were used. chi(2)-Analysis and Fisher's exact test were used for statistical evaluation. The glutathione S-transferase P1b-1b genotype was found significantly more often in women with recurrent early pregnancy loss than in controls (12% versus 5%, P = 0.03), in particular in those who consumed coffee (P = 0.02) or smoked cigarettes (P = 0.04). Polymorphisms in other glutathione S-transferase and cytochrome P450 genes occurred equally frequently in cases and controls. In conclusion, the occurrence of the glutathione S-transferase P1b-1b genotype, leading to lower glutathione S-transferase Pi enzyme activity and consequently to impaired placental detoxification, may represent a risk factor for recurrent early pregnancy loss.

Abortion, Habitual↗