Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

ACMG Cystic Fibrosis Carrier Screening Work Group, American College of Medical Genetics, Bethesda, Maryland 20814, USA.
Genetics in Medicine (Impact Factor: 6.44). 10/2004; 6(5):387-91. DOI: 10.1097/01.GIM.0000139506.11694.7C
Source: PubMed

ABSTRACT experiencing challenges in delivering this service. 4 The current CF Foundation patient mutation database includes nearly double the number of CF patient chromosomes available for analysis in 2000. This report summarizes the major recom- mendations of our Working Group with the supporting justi- fication for these decisions. A number of articles in this issue of Genetics in Medicine provide some of the data on which our decisions were made, whereas others provide new information related to this topic.

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Available from: Victoria M Pratt, Jul 05, 2015
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    ABSTRACT: Cystic Fibrosis (CF) is an autosomal recessive disorder affecting the chloride transport in mucus-producing epithelial cells. The disease is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is responsible for trans-epithelial chloride transport. Approximately 1900 mutations and gene variants of the CFTR have been described. The spectrum of major White-European mutations includes F508del, G542X, G551D and N1303K. F508del is the most common CF-causing mutation, found in approximately 70% of all CF patients worldwide. The spectrum of CF mutations of Arab populations is under-investigated. However, initial molecular-epidemiological studies indicate the existence of specific CF mutation clusters within geographical regions in the Middle East, suggesting specific distributions of CF mutation carrying chromosomes in this part of the world. We showed that the worldwide rare CF mutation S549R is the predominant disease causing mutation in the Omani population. We reported that S549R, together with two other identified mutations, F508del and the rare private mutation V392G, are genetically linked to the exonic methionine polymorphism c.1408A>G; p.Met470Val at exon 10 and the intronic dimorphic 4-bp GATT 6-repeat at intron 6, c.744_33GATT[6_8]. We detected three haplotypes in 28 alleles of the Omani CF cohort and 408 alleles of our control cohort of unrelated and unaffected Omani volunteers. The CF disease associated haplotype consisting of an M allele and a 6-repeat expansion, occurred with an allele frequency of only 0.174 in the normal Omani population. The discriminative power of the haplotype was attributed to the intronic dimorphic 4-bp GATT 6-repeat. Furthermore, we found only one mutation, c.1733_1734delTA in the Omani CF cohort which deviated from the rule and shared the most common haplotype, a V allele and a 7-repeat extension, with the normal population.
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    ABSTRACT: An international working group was established with the aim of making recommendations on the number of offspring for a sperm donor that should be allowable in cases of international use of his sperm. Considerations from genetic, psychosocial, operational and ethical points of view were debated. For these considerations, it was assumed that current developments in genetic testing and Internet possibilities mean that, now, all donors are potentially identifiable by their offspring, so no distinction was made between anonymous and non-anonymous donation. Genetic considerations did not lead to restrictive limits (indicating that up to 200 offspring or more per donor may be acceptable except in isolated social-minority situations). Psychosocial considerations on the other hand led to proposals of rather restrictive limits (10 families per donor or less). Operational and ethical considerations did not lead to more or less concrete limits per donor, but seemed to lie in-between those resulting from the aforementioned ways of viewing the issue. In the end, no unifying agreed figure could be reached; however the consensus was that the number should never exceed 100 families. The conclusions of the group are summarized in three recommendations. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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    ABSTRACT: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene accounts for an autosomal recessive condition called cystic fibrosis (CF). In the Indian subcontinent, CF and its related diseases are under-diagnosed by the medical community due to the poor knowledge of the disease and its confounding diagnosis, and also due to the poor medical facilities available for these patients, thus causing an increased infant mortality rate with a low life expectancy in general. The aim of the study was to document the spectrum and distribution of CFTR mutations in controls, asthma and chronic pancreatitis cases of Northen India. A total of 800 subjects including 400 controls, 250 asthma cases and150 chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D, R117H, W1282X, and S549N) and IVS8 Tn polymorphism. Out of 800 subjects, 18% [(Asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)] were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases while F508del mutation in chronic pancreatitis cases. The carrier frequency of F508del, G542X, G551D, R117H, S549N and T5 were 0.015, 0.025, 0.02, 0.005, 0.005, and 0.022 respectively. The cumulative carrier frequency was 0.093. CFTR mutations were underestimated in Indian population. The present study will serve in establishment of genetic screening and prenatal setup for Indian population.
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