Search results for "Proband"
showing 10 items of 99 documents
Rapid screening of the LDL receptor point mutation FH-Genoa/Palermo
1999
The LDL-receptor gene point mutation FH-Genoa/Palermo is the most frequent mutation responsible for Familial Hypercholesterolemia in Sicily. The mutation does not introduce or abolish any useful restriction site. We establish a GeneComb™-based strategy to identify this mutation in a population of Sicilian unrelated clinically diagnosed FH probands. The method was very sensitive and specific; 12 out of 90 (13.3%) unrelated FH probands were found to carry the FH-Genoa/Palermo mutation. According to these results, the FH-Genoa/Palermo is the more frequent LDL-receptor gene mutation among the Sicilian FH patients. Moreover FH-Genoa/Palermo is the mutation cluster to date more represented in Sou…
Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis
2001
Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 1…
Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.
2006
Patients homozygous or Compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels. more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype. We sequenced Apo B and PCSK9 genes in two patients with the clinical diagnosis of homozygous FH who were heterozygous for LDLR gene mutations. Proband Z.P. (LDL-C 13.39 mmol/L and pCAD) was heterozygous for an LDLR mutation (p.E228K) inherited from her father (LD…
HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS
2008
Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) …
BBS1 Mutations in a Wide Spectrum of Phenotypes Ranging From Nonsyndromic Retinitis Pigmentosa to Bardet-Biedl Syndrome
2012
OBJECTIVE: To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa (RP). METHODS: Homozygosity mapping of a patient with isolated RP was followed by BBS1 sequence analysis. We performed restriction fragment length polymorphism analysis of the p.M390R allele in 2007 patients with isolated RP or autosomal recessive RP and in 1824 ethnically matched controls. Patients with 2 BBS1 variants underwent extensive clinical and ophthalmologic assessment. RESULTS: In an RP proband who did not fulfill the clinical criteria for BBS, we identified a large homozygous region encompassing the BBS1 gene, which carrie…
Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families.
2006
Summary: Purpose: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. Methods: Sixteen families were examined. Probands …
Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other…
2008
Contains fulltext : 69677.pdf (Publisher’s version ) (Closed access) A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large ra…
Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD
2008
Contains fulltext : 70183.pdf (Publisher’s version ) (Closed access) Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identi…
Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors
2010
Contains fulltext : 89304.pdf (Publisher’s version ) (Open Access) CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. OBJECTIVES: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhi…
ATP1A2 mutations in 11 families with familial hemiplegic migraine.
2005
Abstract Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with aura. The disease is caused by mutations of at least three genes among which two have been identified, CACNA1A and ATP1A2. Very few mutations have been identified so far in ATP1A2. We screened the coding sequence of ATP1A2 in 26 unrelated FHM probands in whom CACNA1A screening was negative. A total of eight different mutations were identified in 11 of the probands (41%), including six missense mutations, one small deletion leading to a frameshift, and one in frame deletion. All were novel mutations. Two mutations were recurrent, in three and two families, respectively. Genotyping of 94 relatives of th…