Cystic fibrosis mutational spectrum and genotypic/phenotypic features in Greek‐Cypriots, with emphasis on dehydration as presenting symptom

Yiallouros, Panayiotis K.; Neocleous, Vassos; Zeniou, Maria; Adamidou, T; Costi, Constantina; Christophi, Costas A.; Tzetis, Maria; Kanavakis, Emmanuel; Deltas, Constantinos

doi:10.1111/j.1399-0004.2007.00760.x

Cited by 21 publications

(19 citation statements)

References 12 publications

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“…The most common mutation is F508del, previously termed ΔF508, which accounts for approximately two thirds of all CFTR alleles in patients with CF, with a decreasing prevalence from Northwest to Southeast Europe [5][6][7][8][9][10]. The remaining third of alleles are substantially heterogeneous, with fewer than 20 mutations occurring at a worldwide frequency of more than 0.1% [4,11].…”

Section: Distribution Of Mutationsmentioning

confidence: 99%

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Castellani

Cuppens

Maçek

et al. 2008

Journal of Cystic Fibrosis

530

455

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It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.

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Section: Distribution Of Mutationsmentioning

confidence: 99%

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Castellani

Cuppens

Maçek

et al. 2008

Journal of Cystic Fibrosis

530

455

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“…All patients are from the area of Pafos near the west coast, geographically clustered in a triangle of three neighboring villages. 44 For a recessive disorder, a classic example is the CFTR mutation F508del, with a carrier frequency of 1:14 in the village of Athienou, near Nicosia, the CLINICAL RESEARCH www.jasn.org capital 36 (for an extensive description of founder effects in Cyprus, see Deltas 38 ).…”

Section: Mutation Screening Dna Sequencing and Founder Effectsmentioning

confidence: 99%

COL4A3/COL4A4 Mutations Producing Focal Segmental Glomerulosclerosis and Renal Failure in Thin Basement Membrane Nephropathy

Voskarides¹,

Damianou²,

Neocleous³

et al. 2007

Journal of the American Society of Nephrology

190

178

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Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in ϳ40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis.

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“…The phenomenon of founder effect is not unusual in the Hellenic population of Cyprus and several recent reports have documented several founder mutations in the island. Best examples are the high frequency of 1:14 for CFTR gene mutation F508del observed in a nearby village close to the capital city of Nicosia (Yiallouros et al, 2007), the frequency of 1:7 to 1:10 for Friedreich Ataxia in two villages west of Cyprus close to the city of Paphos (Dean et al, 1988) and the recently reported novel COL4A4 gene mutation G871C in a cohort of Greek Cypriot families with thin membrane nephropathy and Focal Segmental Glomerulosclerosis (Deltas et al, 2011;Voskarides et al, 2008).…”

Section: Discussionmentioning

confidence: 97%

Duplication of exons 3–10 of the HSD17B3 gene: A novel type of genetic defect underlying 17β-HSD-3 deficiency

Neocleous

Sismani

Shammas

et al. 2012

Gene

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Cystic fibrosis mutational spectrum and genotypic/phenotypic features in Greek‐Cypriots, with emphasis on dehydration as presenting symptom

Cited by 21 publications

References 12 publications

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

COL4A3/COL4A4 Mutations Producing Focal Segmental Glomerulosclerosis and Renal Failure in Thin Basement Membrane Nephropathy

Duplication of exons 3–10 of the HSD17B3 gene: A novel type of genetic defect underlying 17β-HSD-3 deficiency

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