Molecular Epidemiology of Phenylalanine Hydroxylase Deficiency in Southern Italy: a 96% Detection Rate with Ten Novel Mutations

Daniele, Aurora; Cardillo, Giuseppe; Pennino, Cinzia; Carbone, Maria Teresa; Scognamiglio, Domenico; Correra, Antonio; Pignero, A; Castaldo, Giuseppe; Salvatore, Francesco

doi:10.1111/j.1469-1809.2006.00328.x

Cited by 37 publications

(24 citation statements)

References 27 publications

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“…In addition, CGH can be used to analyse chromosomal alterations associated with gain or loss of DNA thereby becoming a complementary approach to karyotyping [23]; 3) Southern blot, long PCR or capillary electrophoresis to assess microsatellite expansion typically found in Huntington's disease [24], fragile X syndrome [25], Friedreich's ataxia [26], DM1 [15], and spinocerebellar ataxia [21]. Furthermore, laboratories must be equipped to perform functional studies to define the pathogenicity of novel mutations [16,27] particularly frequent in X-linked diseases [28].…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre

Maruotti

Frisso²,

Calcagno

et al. 2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre

Maruotti

Frisso²,

Calcagno

et al. 2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…For these reasons we selected a population of severely obese young adult patients. Furthermore, it is of note that the population of Southern Italy, from a genetic viewpoint, is highly heterogenous showing differences from other Italian and European regions [31] .…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of the Adiponectin Gene in Severely Obese Patients from Southern Italy

et al. 2008

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Background: Severe obesity is a major worldwide public health concern affecting 0.5–5% of the adult population. Adiponectin (Acpr30), an adipokine secreted from adipocytes, shows pleiotropic beneficial effects on obesity and related disorders. In this study, sequence analysis of Acpr30 gene (ACDC) was performed in a highly selected population of severely obese young adult patients from Southern Italy to investigate the associations between polymorphisms in the ACDC gene and the development of severe obesity concomitantly with other features of the metabolic syndrome. Methods: The ACDC gene was analyzed by direct sequencing in the severely obese patients (n = 220) and compared to healthy controls (n = 116). The associations between the ACDC gene single-nucleotide polymorphisms (SNPs) and the levels of serum Acpr30 as well as the correlation with the presence of severe obesity jointly associated with other features of the metabolic syndrome were also investigated. Total serum Acpr30 concentrations were measured by the ELISA method. Results: ACDC gene molecular screening revealed the presence of previously described SNPs and a new nucleotide alteration, c.355T>G, leading to a protein variant, p.L119V. Measurement of serum concentration of Acpr30 demonstrated lower levels of Acpr30 in the obese population compared to controls (30.5 ± 28.3 vs. 43.9 ± 35.7 μg/ml, p < 0.01); in particular, significantly lower Acpr30 concentrations were observed in obese patients bearing c.–11377C>G SNP CG+GG genotypes than in those with CC genotype (22.9 ± 20.5 vs. 33.1 ± 29.4 μg/ml, p < 0.05). Conclusions: Our results confirmed that low serum levels of Acpr30 are related to severe obesity and a difference in protein expression is associated with variants in ACDC gene promoter region.

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“…Moreover, for other monogenic diseases such as cystic fibrosis and hyperphenylalaninaemia, genes inherited independently of the disease gene could modulate the clinical phenotype [35,36].…”

Section: Genetic Analysis Of Prothrombotic Variantsmentioning

confidence: 99%

Mutational spectrum of F8 gene and prothrombotic gene variants in haemophilia A patients from Southern Italy

et al. 2008

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Haemophilia A (HA) is an X-linked recessive haemorrhagic disorder caused by a deficiency of coagulation factor VIII. Disease causative mutations are heterogeneous and spread all over the F8 gene sequence, with the exception of intron 22 inversion occurring in about 50% of severe patients. To define the specific mutational repertoire and mutation detection rate, we analysed F8 gene, by polymerase chain reaction and direct sequencing, in 128 unrelated patients from Southern Italy with severe (n = 108), moderate (n = 9) or mild (n = 11) HA. We identified 120 mutations, including 64 cases of intron 22 inversion (53.3%), three of intron 1 inversion (2.5%), one large deletion (0,8%) and 52 point mutations (43.3%). In particular, 19/120 were novel and 7/52 point mutations (13.5%) occurred at CpG sites. We also investigated eight prothrombotic genetic variants in a subgroup of 74 severe HA patients to evaluate their possible protective effect on the severity of clinical expression. Methylenetetrahydrofolate reductase A1298C and plasminogen activator inhibitor-1 4G variants recurred more frequently in HA patients with a less-severe phenotype. Clinical impact of these findings needs large-scale studies to further define the role of these prothrombotic variants as possible modifier factors of HA phenotype.

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Molecular Epidemiology of Phenylalanine Hydroxylase Deficiency in Southern Italy: a 96% Detection Rate with Ten Novel Mutations

Cited by 37 publications

References 27 publications

Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre

Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre

Molecular Analysis of the Adiponectin Gene in Severely Obese Patients from Southern Italy

Mutational spectrum of F8 gene and prothrombotic gene variants in haemophilia A patients from Southern Italy

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