Dataset Information

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

ABSTRACT: Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.

SUBMITTER: Lanternier F

PROVIDER: S-EPMC2292130 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

Lanternier Fanny F Cohen-Akenine Annick A Palmerini Fabienne F Feger Frédéric F Yang Ying Y Zermati Yael Y Barète Stéphane S Sans Beatrix B Baude Cédric C Ghez David D Suarez Felipe F Delarue Richard R Casassus Philippe P Bodemer Christine C Catteau Adeline A Soppelsa Frédérique F Hanssens Katia K Arock Michel M Sobol Hagay H Fraitag Sylvie S Canioni Danièle D Moussy Alain A Launay Jean Marie JM Dubreuil Patrice P Hermine Olivier O Lortholary Olivier O

PloS one 20080409 4

Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis ...[more]

PMID: 18404201

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Project description:ObjectiveSeveral theoretical typology models have been proposed to classify alcoholism into more homogeneous subtypes using various criteria, for which age at onset of alcohol dependence is shared across many models. We investigated the evidence for the distinction between early- versus late-onset alcoholism by examining relevant phenotypic and genotypic variables.MethodData are from 1,248 individuals with alcohol dependence, who were interviewed to collect detailed clinical information. Early versus late onset of alcohol dependence was defined by the age at onset of 22 years. Odds ratio (OR) and Cohen's d were calculated as effect size for comparisons of clinical features between the two groups. We adjusted interviewed age and gender in logistic regression models. Case-control genetic analyses were conducted for the association between HTR1B, SLC6A4, DRD2, and OPRμ1 genes and subgroups of alcohol dependence using a sample of 530 controls screened for alcohol problems.ResultsEarly-onset alcoholism exhibited significantly (p < .01) different clinical characteristics from late-onset alcoholism, including higher severity in alcohol dependence symptoms (d = 0.22) and maximum drinking quantity within 24 hours (d = 0.40), more rapid progression from regular drinking to meet alcohol dependence diagnosis (d = 1.73), higher expectancies for alcohol (d = 0.22-0.47), more comorbidity with externalizing disorders (ORs = 2.8-2.9), and greater prevalence of family alcohol use problems (d = 0.26-0.43). In addition, markers in the HTR1B and OPRμ1 genes showed genetic associations with subgroups of alcohol dependence (ORs = 1.5-2.4).ConclusionsOur findings support that subgroups of alcohol dependence defined by onset age have phenotypic and genetic differences. The early-onset subgroup had more severe features for almost every aspect we examined. Coupled with genetic association findings, age at onset of alcohol dependence may serve as a simple but important clinical marker with implications for future etiological research and intervention.

Project description:Although SCN1A variants result in a wide range of phenotypes, genotype-phenotype associations are not well established. We aimed to explore the phenotypic characteristics of SCN1A associated seizure diseases and establish genotype-phenotype correlations. We retrospectively analyzed clinical data and results of genetic testing in 41 patients carrying SCN1A variants. Patients were divided into two groups based on their clinical manifestations: the Dravet Syndrome (DS) and non-DS groups. In the DS group, the age of seizure onset was significantly earlier and ranged from 3 to 11 months, with a median age of 6 months, than in the non-DS group, where it ranged from 7 months to 2 years, with a median age of 10 and a half months. In DS group, onset of seizures in 11 patients was febrile, in seven was afebrile, in two was febrile/afebrile and one patient developed fever post seizure. In the non-DS group, onset in all patients was febrile. While in the DS group, three patients had unilateral clonic seizures at onset, and the rest had generalized or secondary generalized seizures at onset, while in the non-DS group, all patients had generalized or secondary generalized seizures without unilateral clonic seizures. The duration of seizure in the DS group was significantly longer and ranged from 2 to 70 min (median, 20 min), than in the non-DS group where it ranged from 1 to 30 min (median, 5 min). Thirty-one patients harbored de novo variants, and nine patients had inherited variants. Localization of missense variants in the voltage sensor region (S4) or pore-forming region (S5-S6) was seen in seven of the 11 patients in the DS group and seven of the 17 patients in the non-DS group. The phenotypes of SCN1A-related seizure disease were diverse and spread over a continuous spectrum from mild to severe. The phenotypes demonstrate commonalities and individualistic differences and are not solely determined by variant location or type, but also due to functional changes, genetic modifiers as well as other known and unknown factors.

Project description:BackgroundCo-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs).MethodsThe medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated.ResultsSeventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE.ConclusionsCo-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Dataset Information

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

Publications

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

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