17 research outputs found
Distribution of serum lipids and lipoproteins in patients with beta thalassaemia major; an epidemiological study in young adults from Greece
BACKGROUND: Beta-thalassaemia major (b-TM) has been defined as a combination of chronic hemolytic anemia, iron storage disease and myocarditis, and it has been associated with premature death especially due to heart failure. To the best of our knowledge the status of blood lipids in these patients has rarely been investigated. Thus, we assessed the levels of lipids and lipoproteins in a sample of cardiovascular disease free adult men and women with b-TM. METHODS: During 2003 we enrolled 192 consecutive patients with b-TM that visited our Institution for routine examinations. The Institution is considered the major reference center for b-TM in Greece. Of the 192 patients, 88 were men (25 ± 6 years old) and 104 women (26 ± 6 years old). Fasting blood lipid levels were measured in all participants. RESULTS: Data analysis revealed that 4% of men and 2% of women had total serum cholesterol levels > 200 mg/dl, and 11% of men and 17% of women had triglyceride levels > 150 mg/dl. In addition, mean HDL cholesterol levels were 32 ± 11 mg/dl in men and 38 ± 10 mg/dl in women, lipoprotein-a levels were 8.3 ± 9 mg/dl in men and 8.8 ± 9 mg/dl in women, apolipoprotein-A1 levels were 111 ± 17 mg/dl in men and 123 ± 29 mg/dl in women, and apolipoprotein-B levels were 60 ± 20 mg/dl in men and 59 ± 14 mg/dl in women. Total-to-HDL cholesterol ratios were 3.7 ± 1.2 and 3.8 ± 1.5 in men and women, respectively. CONCLUSIONS: The majority of the patients had blood lipid levels (by the exception of HDL-cholesterol) within the normal range, and consequently the prevalence of lipid and lipoprotein abnormalities was much lower as compared to the general population of the same age. Interestingly, is that the total – to HDL cholesterol ratio was high in our patients, and may underline the importance of this index for the prognosis of future cardiac events in these patients
The TREAT-NMD DMD global database: Analysis of more than 7,000 duchenne muscular dystrophy mutations
Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)
The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.
Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)
239-kb Microdeletion Spanning KMT2E in a Child with Developmental Delay: Further Delineation of the Phenotype
Pathogenic KMT2E variants underly O'Donnell-Luria-Rodan syndrome, a
recently described neurodevelopmental disorder characterized by global
developmental delay, variable degrees of intellectual disability, and
subtle facial dysmorphism. Less common findings include autism,
seizures, gastrointestinal (GI) problems, and abnormal head
circumference. Occurrence of mostly truncating variants as well as the
similar phenotype observed in individuals with deletions spanning KMT2E
suggest haploinsufficiency of this gene as a common mechanism for the
disorder, while a gain-of-function or dominant-negative effect cannot be
ruled out for some missense variants. Deletions reported in the
literature encompass several additional known or presumed
haploinsufficient genes, thus leading to more complex phenotypes. Here,
we describe a male with antenatal onset hydronephrosis, hypotonia,
global developmental delay, prominent GI symptoms as well as facial
dysmorphism. Chromosomal microarray revealed a 239-kb de novo
microdeletion spanning KMT2E and LHFPL3. Clinical presentation of our
proband, harboring one of the smallest deletions of the region confirms
the core features of this disorder, suggests GI symptoms as a prominent
finding in affected individuals while expanding the phenotypic spectrum
to abnormalities of the urinary tract
Array-CGH revealed one of the smallest 16q21q22.1 microdeletions in a female patient with psychomotor retardation
A 28-month-old girl with dysmorphic craniofacial features, microcephaly,
hypotonia, psychomotor retardation, failure to thrive and
gastrointestinal problems was referred for clinical evaluation.
Array-CGH analysis revealed one of the smallest de novo microdeletions
on chromosome 16q21q22.1, 2.03 Mb in size. Advanced molecular analysis
contributes to more precise genotype-phenotype correlation and accurate
definition of the breakpoints in the deleted/duplicated regions. (C)
2012 European Paediatric Neurology Society. Published by Elsevier Ltd.
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A boy with conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), borderline intellectual disability, and 47,XXY syndrome in combination with a 7q11.23 duplication, 11p15.5 deletion, and 20q13.33 deletion
markdownabstract_Background:_ This is a case with multiple chromosomal aberrations which are likely etiological for the observed psychiatric phenotype consisting of attention deficit hyperactivity and conduct disorders.
_Case presentation:_ We report on an 11 year-old boy, admitted to the pediatric hospital for behavioral difficulties and a delayed neurodevelopmental trajectory. A cytogenetic analysis and high-resolution microarray comparative genomic hybridization (CGH) analysis was performed. The cytogenetic analysis revealed 47,XYY syndrome, while CGH analysis revealed an additional duplication and two deletions. The 7q11.23 duplication is associated with speech and language delay and behavioral symptoms, a 20q13.33 deletion is associated with autism and early onset schizophrenia and the 11p15.5 microdeletion is associated with developmental delay, autism, and epilepsy. The patient underwent a psychiatric history, physical examination, laboratory testing, and a detailed cognitive, psychiatric, and occupational therapy evaluation which are reported here in detail.
_Conclusions:_ In the case of psychiatric patients presenting with complex genetic aberrations and additional psychosocial problems, traditional psychiatric and psychological approaches can lead to significantly improved functioning. Genetic diagnostic testing can be highly informative in the diagnostic process and may be applied to patients in psychiatry in case of complex clinical presentations