The 3849+10 kB C—>T Mutation in a 21-Year-Old Patient with Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the most common lethal inherited disease in the white population. It is characterized by exocrine gland epithelia dysfunction, which leads to pulmonary and pancreatic insufficiency. Since the cloning of the CF gene in 1989 and the identification of the most common CF mutation (ΔF508), more than 400 different mutations have been described. These mutations appear to contribute to the heterogeneity of the CF phenotype and several reports have speculated on the relationship between the most common CF mutations and the patient's clinical status.

We report the case of a 21-year-old woman with longstanding chronic pansinusitis, nasal polyposis, chronic cough and severe nasal crusting. During a period of five years she had been followed by her otolaryngologist and pediatric pulmonologist. Sweat tests performed at the age of 17 and 18 were within normal limits and she underwent repeated conventional sinonasal procedures, with no improvement in her clinical status. On her present admission, sweat tests showed a 70 meq/l chloride concentration. The diagnosis of CF was then confirmed by DNA analysis and the patient was found to carry the 3849+10 kB C—>T mutation. The early detection of this newly recognized form of CF in adults as well as in children presenting with sinonasal symptoms is critical for life expectancy and quality.

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References

McQuitty

J.C.

, Lewis

N.C.

Cystic fibrosis, in Rudolph

A.M.

, Hoffman

J.I.E.

, Rudolph

C.D.

(eds): Rudolph Pediatrics. Norwalk, Connecticut/San Mateo, California, Appleton & Lange 1991; 27–33.

Kerem

, Rommens

J.M.

, Buchanan

J.A.

Identification of the Cystic Fibrosis gene: Genetic analysis. Science 1989; 1073–80.

Augarten

, Kerem

B.S.

, Yahav

Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849+10 kB C → T mutation. Lancet 1993; 342: 24–5.

Kawasaki

E.S.

Sample preparation from blood, cells and other fluids, in Innis

M.A.

, Gelfand

D.H.

, Sninski

J.J.

(eds): PCR protocols: A guide to methods and applications. San Diego, California, Academic Press, Inc. 1990; 146–52.

Abeliovich

, Lavon

I.P.

, Lerer

Screening for five mutations detects 97% of cystic fibrosis chromosomes and predicts a carrier frequency of 1: 29 in the Jewish Ashkenazi population. Am J Hum Genet 1992; 51: 951–6.

Shwachman

, Kulczycki

L.L.

, Mueller

H.L.

Nasal polyposis in patients with cystic fibrosis. Pediatrics 1962; 30: 389–401.

Rulon

J.T.

, Brown

H.A.

, Logan

G.B.

Nasal polyps and cystic fibrosis of the pancreas. Arch Otolaryngol 1963; 78: 192–9.

Stern

R.C.

, Boat

T.F.

, Wood

R.E.

Treatment and prognosis of nasal polyps in cystic fibrosis. Am J Dis Child 1982; 136: 1067–70.

Cepro

, Smith

R.J.H.

, Caltin

F.I.

Cystic fibrosis — An otolaryngologic perspective. Otolaryngol Head and Neck Surg 1987; 97: 356–60.

10.

Gharib

, Allen

R.P.

, Juus

H.A.

Paranasal sinuses in cystic fibrosis: Incidence of roentgen abnormalities. Am J Dis Child 1964; 108: 499–502.

11.

Riordan

J.R.

, Rommens

J.M.

, Kerem

Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1989; 245: 1066–73.

12.

Rommens

J.M.

, Iannuzzi

M.C.

, Kerem

Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science 1989; 245: 1059–65.

13.

Cystic Fibrosis Genetic Analysis Consortium World wide survey of the ΔF508 mutation — Report from the Cystic Fibrosis Genetic Analysis Consortium. Am J Hum Genet 1990; 47: 354–9 (Letter).

14.

Kerem

, Corey

, Kerem

B.S.

The relation between genotype and phenotype in cystic fibrosis — analysis of the most common mutation (ΔF508). N Eng J Med 1990; 323: 1517–22.

15.

Santis

, Osborne

, Knight

R.A.

Linked marker haplotypes and the ΔF508 mutation in adults with mild pulmonary disease and cystic fibrosis. Lancet 1990; 335: 1426–9.

16.

Shoshani

, Augarten

, Gazit

Association of nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet 1992; 50: 222–8.

17.

Highsmith

W.E.

, Burch

L.H.

, Boat

T.F.

Identification of a homozygous point mutation in intron 19 in an inbred CF patient with a mild disease and normal sweat chloride: Creation of an alternative splice site resulting in base sequence insertion in CFTR coding region between exon 19 and 20. Pediatr Pulmonol Suppl 1991; 6: 22A.