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L Galli

Publications and source records attributed to L Galli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Thyroid function in children with perinatal human immunodeficiency virus type 1 infection.

OBJECTIVE: To study thyroid function in children with perinatal HIV-1 infection retrospectively and determine whether thyroid abnormalities are correlated with clinical condition, disease progression, immunological impairment, and viral load. STUDY DESIGN AND SETTING: Total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine, reverse triiodothyronine (rT3), thyrotropin (TSH), thyroglobulin (TG), and thyroid binding globulin (TBG) were measured twice in 56 children with perinatal human immunodeficiency virus type 1 (HIV-1) infection. Median age at first determination was 13.5 (range: 0.03-127.0) months; median age at second determination was 66.2 (range 3.42-147.4) months. Antithyroglobulin, antimicrosomal, thyroid peroxidase, and thyrotropin receptor antibodies were also evaluated. Fifty-three healthy children were selected as controls. RESULTS: TT3, TT4, FT4, and TG were significantly reduced and rT3, TBG, and TSH increased in children with HIV-1 infection when compared with controls. Thyroid dysfunction correlated with severe immunosuppression and high viral load early in life preceded the onset of the disease and worsened over time. Autoantibodies were negative in all children with HIV-1 infection in all determinations. CONCLUSION: Thyroid abnormalities are observed early in the course of perinatal HIV-1 infection; thyroid dysfunction is particularly pronounced in children with severe immunosuppression and high viral load. Modifications of thyroid function precede worsening of clinical course in HIV-1 infected children.

CD4 Lymphocyte Count↗
PubMed2000

Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children.

BACKGROUND: To compare the Centers for Disease Control and Prevention (CDC) paediatric classification system with the long-term course of perinatal human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Prospective study on 366 perinatally infected children followed-up from birth and checked at least every 2 months. Survival, smoothed hazard, adjusted hazard ratio of death, and transition probabilities in clinical and immunological categories were outcome measures. RESULTS: Survival was 49% (95% CI : 40-58%) at 8 years. The risk of death was high before the age of 2, relatively low between ages 2 and 7, and contained thereafter. Children did not advance through the categories sequentially. Survival at 8 years was 61.7% (95% CI : 49.8-73.6%) in those children who had passed through clinical category A; the hazard ratio of death was 2.5 (95% CI : 1.7-3.8) for 175 (47.9%) children who skipped this category. Transition probability in clinical category B was 39.9% (95% CI : 32.3-45.6%) after one year, but 59.1% (95% CI : 51.4-66.8%) after 5 years. Before 2 years of age, the probability of entry into category C (40%; 95% CI : 35-45%) was higher than that of entry into immunological category 3 (28%; 95% CI : 22-34%). Conclusions The classification system stands comparison with the clinical reality, but the CD4-positive cell thresholds in infancy should be adjusted and category B indicator diseases better distributed to improve their predictive value.

CD4 Lymphocyte Count↗
PubMed2000

Ambamustine in the second-line treatment of patients with small-cell lung cancer: a phase II Fonicap study.

Despite a high probability of response to first-line chemotherapy, most patients with small-cell lung cancer (SCLC) will eventually have progression of their disease because of the development of resistant disease. Second-line testing of new drugs is an accepted research strategy in SCLC. In this context, the Italian Lung Cancer Task Force (FONICAP) has tested a new synthetic bifunctional alkylating agent, Ambamustine, with preliminary evidence of activity in other solid tumors. Patients with measurable SCLC, progressive after one first-line chemotherapy regimen (either "sensitive" or "refractory"), were eligible for the study. Ambamustine was administered at the dose of 2 mg/kg as a 1-hour intravenous infusion on day 1 every 21 days. The dose was to be increased to 3 mg/kg if no grade IV toxicity and complete hematologic recovery had occurred by day 22. Sample size was calculated according to a two-stage optimal Simon's design. Seventeen patients were entered into the study. Twelve patients were refractory to prior chemotherapy; 12 had extensive disease; the median age was 64 years (range: 46-75 years) and the median performance status was 1. Among 13 patients who received more than one cycle, 9 patients could increase Ambamustine dose from 2 to 3 mg/kg. No objective response was observed: one patient obtained a 50% regression of the primary tumor with contemporary disease progression in the liver and was qualified as having progressive disease. The treatment was well tolerated: grade IV leukopenia occurred in only 1 patient; grade III anemia occurred in 17.6%, grade III leukopenia in 11.8%, and grade III thrombocytopenia in 23.5%. Nonhematologic toxicity was minimal. Ambamustine, at the dose and schedule used in this study, is well tolerated in pretreated patients with SCLC but has no significant antitumor activity in this unfavorable group of patients.

Aged↗
PubMed2000

Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors.

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.

Abdominal Pain↗
PubMed2000

A retrospective analysis of postradiation chemotherapy in 133 patients with glioblastoma multiforme.

The impact on survival of postradiation nitrosourea-containing chemotherapy (CHT) in patients with glioblastoma multiforme (GM) was analyzed retrospectively in 133 patients who completed the planned radiotherapy out of 173 observed cases. Thirty-five patients were < 50 years old, 89 were males, 20 had performance status (PS) < 70 and 72 > or = 70. Surgery was followed by radiotherapy in all cases (50-60 Gy in 95 patients, 61-70 Gy in 38 patients). At the end of radiotherapy, 43 patients received CHT, whereas 90 patients did not receive further therapy. At univariate analysis, age < 50 years, feminine gender, subtotal or total resection, radiotherapy doses > 60 Gy, and CHT had an independent prognostic value. Our results suggest that chemotherapy improves 2-year survival rates from 12% to 28% in GM. The sequence of treatment, new drugs, and combinations should be further explored.

Adult↗
PubMed2000

The role of vitamin B12 in fasting hyperhomocysteinemia and its interaction with the homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. A case-control study of patients with early-onset thrombotic events.

Total fasting plasma homocysteine (tHcy), homozygosity for the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and for the A2756G mutation of the methionine synthase (MS) gene, vitamin B12 and folate plasma levels were evaluated in 170 consecutive patients (89 M, 81 F; mean age 41 +/- 12 yrs) with documented early-onset thrombosis (89 venous, 69 arterial, 12 both; mean age at first episode 36 +/- 11 yrs), and in 182 age- and sex-matched healthy control subjects. Moderate hyperhomocysteinemia (HHcy, tHcy >19.5 microM in men and >15 microM in women) was detected in 45 patients (26.5%) and in 18 controls (9.9%, Mantel-Haenszel OR and 95% C.I. after stratification for arterial or venous thrombosis: 3.25, 1.78-5.91). The 677TT MTHFR genotype was not significantly more prevalent in patients (27.6%) than in controls (21.4%, RR = 1.42: 0.84-2.41), and markedly contributed to HHcy (Mantel-Haenszel RR after stratification for case/control status: 8.29, 4.61-14.9). The 2756GG MS genotype, observed in 4 patients (2.4%) and 8 controls (4.4%), was not associated to HHcy. tHcy was negatively correlated to folate and vitamin B12 levels, with better correlation found in subjects with the 677TT mutation (r = -0.42 and -0.25) than with the 677CC or CT MTHFR genotype (r = 0).37 and -0.11). However, folate was similar in patients and controls and vitamin B12 was higher in patients (460 +/- 206 vs. 408 +/-185 pg/ml, p = 0.011). In a generalized linear model, 44% of the variation in tHcy levels was explained by folate and vitamin B12 levels, the MTHFR genotype, gender, and by the interaction of the MTHFR genotype with folate (p < or =0.028); the interactions of vitamin B12 with the MTHFR genotype, gender and patient/control status also significantly contributed to the variation in tHcy levels (p < or =0.028). A 4-week administration of 5-methyltetrahydrofolate (15 mg/day) markedly lowered plasma tHcy in 24 patients with MTHFR 677TT genotype, but the response to treatment correlated with vitamin B,2 levels (p = 0.023). Subjects carrying the MTHFR 677TT genotype have higher folate and vitamin B12 requirements irrespective of the A2756G polymorphism of the MS gene. Yet unidentified abnormalities of MS or of any of the enzymes participating in the synthesis of methylated vitamin B12 may play an important role in the phenotypic expression of moderate hyperhomocysteinemia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1999

Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c.

Glycogen storage diseases type 1 (GSD 1) are a group of autosomal recessive disorders characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Mutations of the glucose-6-phosphatase gene are responsible for the most frequent form of GSD 1, the subtype 1a, while mutations of the glucose-6-phosphate transporter gene (G6PT) have recently been shown to cause the non 1a forms of GSD, namely the 1b and 1c subtypes. Here, we report on the analysis by single-stranded conformation polymorphism (SSCP) and/or DNA sequencing of the exons of the G6PT in 14 patients diagnosed either as affected by the GSD 1b or 1c subtypes. Mutations in the G6PT gene were found in all patients. Four of the detected mutations were novel mutations, while the others were previously described. Our results confirm that the GSD 1b and 1c forms are due to mutations in the same gene, i.e. the G6PT gene. We also show that the same kind of mutation can be associated or not with evident clinical complications such as neutrophil impairment. Since no correlation between the type and position of the mutation and the severity of the disease was found, other unknown factors may cause the expression of symptoms, such as neutropenia, which dramatically influence the severity of the disease.

Antiporters↗
PubMed1999

Interleukin-6 synthesis and IgE overproduction in children with perinatal human immunodeficiency virus-type 1 infection.

BACKGROUND: Unbalanced interleukin network and elevated IL-6 synthesis are suggested mechanisms of immunoglobulin overproduction in children with perinatal human immunodeficiency virus-type 1 (HIV-1) infection. OBJECTIVE: To investigate whether elevated IL-6 synthesis is a general mechanism of immunoglobulin overproduction in perinatal HIV-1 infection. METHODS: In vitro spontaneous and phytohaemoagglutinin (PHA)-stimulated IL-6 and IL-2 synthesis, serum IgE, IgG, IgA, and IgM levels, CD4+ T-lymphocyte counts, and HIV-1 RNA copy numbers were cross-sectionally determined in 31 children with perinatal HIV-1 infection. Children with immunoglobulin z-scores in the highest quartile were defined as children with high immunoglobulin level. Relationships between interleukin synthesis, high immunoglobulin levels, and HIV-1 related disease were studied. RESULTS: Children with high IgE levels had higher spontaneous IL-6 synthesis (1337 +/- 138 pg/mL) compared with those without high IgE levels (861 +/- 194 pg/mL; P < .001). By contrast, spontaneous IL-6 synthesis was similar in children with or without high IgG, IgA, or IgM levels. Decreased PHA-stimulated IL-2 synthesis, low CD4+ lymphocyte counts, elevated HIV-1 RNA copy numbers, and severe disease correlated with high IgE (but not IgG, IgA, and IgM) levels. IgG, IgA, and IgM levels correlated with each other, but not with IgE levels. CONCLUSION: The increased IL-6 synthesis in HIV-1+ children may affect IgE rather than other immunoglobulin isotype levels. Overall results suggest that IgE and IgG, IgA, IgM overproduction have distinct underlying mechanisms.

CD4 Lymphocyte Count↗
PubMed1999

Low IgG3 and high IgG4 subclass levels in children with advanced human immunodeficiency virus-type 1 infection and elevated IgE levels.

BACKGROUND: IgG3 and IgG4 levels are not always changed in children perinatally infected with human immunodeficiency virus-type 1 (HIV-1). Elevated IgE levels hallmark the TH1 to TH2 switch occurring in advanced infection and such an unbalanced cytokine network may affect the IgG subclass production. OBJECTIVE: To examine the different behaviour of IgG3 and IgG4 in the light of elevated IgE levels. METHODS: IgE and IgG subclass levels were cross-sectionally determined (by radioimmunoassay and enzyme-linked immunosorbent assay, respectively) in 54 HIV-1 perinatally infected children. IgE levels beyond the upper 95% confidence limits (95%CL) of the age-related reference values defined elevated IgE levels. Since immunoglobulin levels physiologically vary with age, individual z-scores of isotype levels were calculated using the upper 95%CL of age-related reference values. RESULTS: Fifteen (27.7%) children had elevated IgE levels. They had lower IgG3 (mean +/- standard deviation: -1.4+/-0.9 versus 6.9+/-0.9; P < .0001) and higher IgG4 (3.1+/-0.6 versus 0.2+/-0.3; P < .0001) z-scores compared with children without elevated IgE levels. Similar IgG1 (11.7+/-1.8 versus 12.6+/-1.3) and IgG2 (-0.22+/-0.8 versus -0.19+/-0.6) z-scores were found. In children with elevated IgE levels, IgE and IgG3 z-scores inversely correlated (r = -0.867; P < .0001), IgE and IgG4 z-scores directly correlated (r = 0.831; P < .0001) and IgG3 and IgG4 z-scores inversely correlated (r = -0.745; P < .001). CONCLUSION: Low IgG3 and high IgG4 levels may be present in HIV-1 advanced disease with elevated IgE levels. Changes may be in line with the TH1 to TH2 switch and contribute to disease progression.

CD4-Positive T-Lymphocytes↗
PubMed1999

Viral load and CD69 molecule expression on freshly isolated and cultured mitogen-stimulated lymphocytes of children with perinatal HIV-1 infection.

HIV-1 in adults changes the proportion of mitogen-stimulated lymphocytes expressing the CD69 activation molecule, but little is known about this molecule expression on lymphocytes of HIV-1-infected (HIV-1+) children. Freshly isolated CD3+, CD4+, CD8+ and CD19+ and phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes co-expressing CD69 were investigated cross-sectionally (adopting a MoAb double-staining technique) in 24 HIV-1+ children with severe disease and given anti-retroviral therapy and in 24 age-matched healthy children. CD69 results in HIV-1+ children were correlated with plasma HIV-1 RNA load prospectively determined. HIV-1+ compared with healthy children had higher frequencies of freshly isolated CD3+CD69+ (2.4 +/- 2.2% versus 0.9 +/- 0.5%; P = 0.002) and CD8+CD69+ (1.5 +/- 1.1% versus 0. 5 +/- 0.2%; P < 0.0001) lymphocytes. The frequencies of CD4+CD69+ and CD19+CD69+ lymphocytes were similar. High viral load correlated with an elevated proportion of freshly isolated CD3+CD69+ and CD8+CD69+ lymphocytes. HIV-1+ children showed reduced frequencies of PHA-stimulated CD3+CD69+ (60.7 +/- 7.6% versus 86.1 +/- 7.6%; P < 0. 001), CD4+CD69+ (73.6 +/- 18.2% versus 92.6 +/- 5.1%; P < 0.001), and CD8+CD69+ (51.0 +/- 19.1% versus 65.3 +/- 15.4%; P = 0.007) lymphocytes. Virologic worsening within 6 months correlated with a low proportion of PHA-stimulated CD3+CD69+ and CD8+CD69+ lymphocytes. CD69 molecule expression reflected the coexistence of immune activation and immune deficiency in HIV-1 infection. Changes partly differed from those observed in HIV-1+ adults. CD8+CD69+ (but not CD4+CD69+) lymphocyte proportion correlated with virologic course, and an impaired ability of CD8+ lymphocytes to express CD69 upon PHA stimulation preceded a virologic worsening.

Antigens, CD↗
PubMed1999

Prevalence of Helicobacter pylori infection detected by serology and 13C-urea breath test in HIV-1 perinatally infected children.

BACKGROUND: Conflicting results have been reported in adults with human immunodeficiency virus (HIV-1) who were investigated for Helicobacter pylori infection. Most studies indicate a lower prevalence than is found in the general population. The purposes of this study were to evaluate H. pylori prevalence by noninvasive methods in a population of children perinatally infected with HIV-1 and to correlate H. pylori prevalence with HIV-1-related clinical and immunologic status. METHODS: H. pylori infection was studied in 45 children perinatally infected with HIV-1 by performing serologic testing of anti-H. pylori immunoglobulin G antibodies and the 13C-urea breath test. RESULTS: Eight children with HIV-1 (17.7%) were positive by serology, and nine (20%) were positive by 13C-urea breath test. No significant differences related to age, previous antibiotic treatment, immunoglobulin administration, antiretroviral treatment, abdominal pain, CD4+ cell count, number of HIV-1 RNA copies, and frequency of severe immunodepression were noted between children with positive 13C-urea breath test results and those with negative results. Children with positive results were significantly more likely to have severe clinical manifestations. CONCLUSIONS: The results show, by both serology and 13C-urea breath test, a prevalence of H. pylori infection comparable with the prevalence in the normal population of the same age. H. pylori prevalence has probably been underestimated in patients with HIV. Results of serologic and histologic analyses for H. pylori require cautious interpretation, especially in severely immunodeficient patients.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Assessment of CABG-related risk in patients with CAD and LVD. Contribution of PET with [18F]FDG to the assessment of myocardial viability.

BACKGROUND: Previous studies have demonstrated that hibernating myocardium can be assessed by [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). This study evaluated the use of [18F]FDG-PET for CABG related risk assessment in patients with coronary artery disease (CAD) and left ventricle dysfunction (LVD). METHODS: We retrospectively evaluated 241 to patients candidate CABG presenting with signs and symptoms of congestive heart failure (CHF) prevailing over ischemic signs. Of the 241 patients, 153 had undergone [18F]FDG-PET as well as conventional assessment: 110 out of 153 (group A) were operated because of PET evidence of hibernation. Of the 241 patients, 88 had not undergone [18F]FDG-PET: 86 out of 88 (group B) were operated on. The outcome of surgical patients was evaluated by considering all major perioperative complications including the use of mechanical and pharmacological support and in-hospital mortality. After hospital discharge, each patient was examined at 1, 4 and every 6 months thereafter. RESULTS: Perioperative use of mechanical supports and inotropic drugs, was significantly lower for the PET selected group (A) than for the non PET selected group (B). Mortality within 30 days of surgery was 0.9% in group A and 19.8% in group B. The only predictors of perioperative outcome were the presence of hibernating tissue and the ejection fraction. CONCLUSIONS: [18F]FDG-PET prior to CABG can be crucial for the assessment of perioperative risk in patients with CAD.

Coronary Artery Bypass↗
PubMed1999

Psoriatic arthritis in British and Italian patients: a comparative clinical, radiologic, and scintigraphic study.

OBJECTIVE: To investigate the similarities and differences in pattern and severity of clinical expression of psoriatic arthritis (PsA) in British and Italian patients. METHODS: Detailed clinical data were obtained on 48 British patients with PsA and compared with the data of 48 Italian patients. A systematic evaluation of joints, spine, and skin was performed. Forty-one British and 42 Italian patients also underwent a whole body bone scintigram. Radiographic details of hands and wrists were also taken. RESULTS: The Italian patients did not differ from their British counterparts with respect to duration of arthritis, sex, clinical subgroups, axial involvement, number of tender and swollen joints, or radiographic score. However, significant differences were found with respect to age, duration of psoriasis, number of joints with deformity and/or loss of function, number of affected joints, and number of "active" joints on scintigraphy, which were all higher in the British group. After correction for age, duration of arthritis, and duration of psoriasis the only significant difference was the number of affected joints. CONCLUSION: Our findings suggest that British patients with PsA are more severely affected than a matched cohort of Italian patients.

Adult↗
PubMed1998

Zidovudine therapy and HIV type 1 mutations in children with symptomatic HIV type 1 infection: effect of switching to didanosine or zidovudine plus didanosine therapy. Italian Multicenter Study Group on HIV Mutations in Children.

Type and prevalence of zidovudine (ZDV) resistance mutations in HIV-1-infected children in clinically stable condition and on ZDV monotherapy were analyzed to evaluate the effect of switching to didanosine (ddI) monotherapy or to ZDV plus ddI on the pattern of mutations and on the clinical outcome. Monthly clinical and laboratory controls for HIV-1 infection status were performed; at enrollment and every 4 to 6 months after treatment randomization mutant proviral sequences were evaluated in all the children, whereas viral burden was performed only in a small subgroup of patients randomly selected in each of the three treatment groups. ZDV resistance-associated proviral DNA mutations were defined as low-level resistance (LLR) mutations or medium/high-level resistance (MHLR) mutations; clinical outcome was considered as stable or deteriorating. Results showed that at entry into the study the duration of ZDV therapy was significantly correlated with the presence of mutations, and that the level of resistance given by mutations was associated with the severity both of symptoms and immunodeficiency. After randomization to treatment, in patients with mutations that confer LLR a better clinical outcome with ddI monotherapy than with ZDV plus ddI and ZDV alone was observed in the subsequent 6 months, whereas in patients with mutations that confer MHLR no significant difference among the three treatment groups was found. Data showed also that levels of viral burden at the time of changing therapy are related to clinical outcome if measured by plasma viral load. These results suggest that genotypic resistance assays, together with viral load, may prove useful for rational treatment decisions both at the start of therapy and with failure.

Anti-HIV Agents↗
PubMed1998

Horizontal transmission of human immunodeficiency virus type 1 from father to child.

An unusual case of human immunodeficiency virus type 1 (HIV-1) infection in a child was studied. The child, identified as HIV-1 infected at 5 years of age, lived with his parents and a 3-year-old sister. HIV-1 infection was excluded in the mother and sister, but confirmed in the father, who was unaware of his infection and was in good health, apart from an atopic dermatitis on the face and limbs. A portion of the HIV-1 proviral envelope gene was amplified from the father's and child's peripheral blood cells, and the amplified products were cloned and sequenced. Phylogenetic analysis disclosed that the father's and child's viral sequences clustered together, and were clearly distinct from the sequence sets obtained from six epidemiologically unlinked mother-child HIV-1-infected pairs included in the analysis. HIV-1 variability was lower in the child's sequence set than in the father's, and the variability between father's and child's sequences was significantly lower than that found between epidemiologically unlinked cases (p < 0.001). An uncommon APGR motif on the tip of the V3 domain was found in both the father's and child's viral clones. These data, together with the epidemiological investigations, strongly suggest that the child acquired the infection from his father, possibly by exposure to bleeding skin lesions.

Adult↗
PubMed1998

Mosaicism for full mutation and normal-sized allele of the FMR1 gene: a new case.

The main mutation in fragile X patients is the expansion of the CGG repeat in the first exon of the FMR1 gene, associated with hypermethylation of the proximal CpG island. An increasing number of atypical cases have been reported showing the coexistence of full mutation and premutated or normal-sized alleles. These genotypes are more difficult to detect, and if a PCR strategy alone is adopted, they can be incorrectly identified. We report on a fragile X man with severe phenotype and mosaicism for full mutation and a (CGG)7 normal allele, the shortest fragment reported as yet in mosaics. This case of mosaicism, as other similar cases previously reported, suggests that the normal-length allele can derive from a deletion during the same early stage of development in which the full mutation expansion also arose.

Adult↗