Detection of 100% of the CFTR mutations in 63 CF families from Tyrol

Abstract

We identified 100% of the CFTR gene mutations, including three novel mutations, in 126 unrelated cystic fibrosis chromosomes from Tyrol, Austria. The frequency of the major mutation ΔF508 (74.6%) was not significantly different in Tyrolian CF‐patients than in patients from Bavaria (71.0%) and Middle‐and Northern Germany (71.9%), but was significantly higher than in patients from Styria (58.1%) or Northern Italy (47.6%). Interestingly, the distribution of the next most frequent mutations, R1162X (8.7%) 2183AA→G, 2789 +5G→A and G542X (2.4% each), was more similar to the distribution of these mutations among CF‐patients from Northern Italy than to those from Styria, Bavaria or Middle‐and Northern Germany. Nine further mutations occurred once or twice. One of these, the missense mutation M1101K, is rare worldwide but very frequent in the Hutterite brethren, a small founder population which came from Southern Austria to Northern America. Three other different mutations (ΔL453, 1874insT and 4108delT) were present in single Tyrolian families and have not been described before. The identification of 100% of CFTR gene mutations in a particular CF population demonstrates the power of genetic analysis for the diagnosis and counselling of CF families in this restricted geographical area of Austria. Our study provides evidence for a closer genetic relation between CF patients from Tyrol and those from Bavaria or Middle‐and Northern Germany as well as Northern Italy, than between CF patients from the two Austrian states Tyrol and Styria.

Drawing the history of the Hutterite population on a genetic landscape: inference from Y-chromosome and mtDNA genotypes

“…6,7 A 'private' mutation, M1101K, is the more common mutation, whereas DF508 is a less frequent mutation in the Hutterites. Recently, however, the M1101K mutation was reported in a single patient among 63 CF families from the Tyrol region, 8 suggesting that at least one founder from the Tyrol introduced this mutation into the Hutterite population. Owing to founder effects and population expansion, this mutation now accounts for 64% of CF mutations among US and Canadian Hutterite CF families 6 and 82% of CF mutations in a population-based study in South Dakota Hutterites.…”

Clinical genetics and the Hutterite population: A review of Mendelian disorders

“…DNA analysis of one affected Hutterite patient identified the same homozygous mutation (personal observation), suggesting this condition may have arisen in the Hutterite community from a shared Mennonite founder. The M1101K mutation causing CF is very rare worldwide but has been observed in the Tyrol population [Stuhrmann et al, 1997], the area from which the Hutterites originated over 400 years ago. Other populations derived from ancestors that shared part of their history with the Hutterites may also harbor some of the autosomal recessive mutations and/or disorders documented in Table I.…”

CFTR gene mutations in pancreatitis: Frequency and clinical manifestations in an Austrian patient cohort

“…In contrast, a recent study of patients with idiopathic chronic pancreatitis, in whom all exons and exon-intron boundaries of the CFTR gene were sequenced, showed that the spectrum of mutations in CP is different and only 35% of CF mutations are identified when mutation analysis for the 29 most common mutations is carried out [13]. Studies of CFTR have been carried out previously in the Austrian region of Tyrol [22], but only in relation to paediatric cohorts with cystic fibrosis and not in adults with pancreatitis. The carrier frequency is 1 in 31 in the different populations of European descent [23].…”