Low prevalence of SPINK1 gene mutations in adult patients with chronic idiopathic pancreatitis

Editor—Chronic idiopathic pancreatitis is a genetically heterogeneous disease.1-3 Mutations of the cationic trypsinogen ( CT ) gene underlie some cases of juvenile pancreatitis,3-5 and mutations of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene have been associated with chronic pancreatitis in adults.6-8 However, these genes account for only a relatively small proportion of cases. More recently, the serine proteinase inhibitor Kazal type 1 ( SPINK1 ) gene, also called PSTI , has attracted attention as a possible cause for chronic pancreatitis.9 10 One study by Chen et al 9 did not find disease causing mutations of SPINK1 among 14 families with hereditary and 30 patients with sporadic pancreatitis, apart from two rare amino acid substitutions which were observed at a comparable frequency to the general population. By contrast, another study by Witt et al 10 reported 23 out of 68 children and adolescents with chronic pancreatitis whose disease was associated with the occurrence of SPINK1 mutations in the heterozygous or homozygous state. In particular, one founder mutation, N34S, was identified in 18/68 German patients …

[1]  M. Manns,et al.  Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation. , 2000, Gastroenterology.

[2]  M. Manns,et al.  Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis , 2000, American Journal of Gastroenterology.

[3]  Olfert Landt,et al.  Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis , 2000, Nature Genetics.

[4]  Fricker,et al.  Mouse model of spinal muscular atrophy. , 2000, Drug discovery today.

[5]  A. Bird,et al.  Confirmation of the assignment of the Sanjad-Sakati (congenital hypoparathyroidism) syndrome (OMIM 241410) locus to chromosome lq42-43 , 2000, Journal of medical genetics.

[6]  Y L Wang,et al.  Duplications and de novo deletions of the SMNt gene demonstrated by fluorescence-based carrier testing for spinal muscular atrophy. , 1999, American journal of medical genetics.

[7]  T. Wienker,et al.  Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. , 1999, American journal of human genetics.

[8]  A. Munnich,et al.  Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis , 1999, Journal of medical genetics.

[9]  D. Parsons,et al.  Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number. , 1998, American journal of human genetics.

[10]  M. Knowles,et al.  Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. , 1998, The New England journal of medicine.

[11]  M. Schwarz,et al.  Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. , 1998, The New England journal of medicine.

[12]  J. Melki,et al.  The role of the SMN gene in proximal spinal muscular atrophy. , 1998, Human molecular genetics.

[13]  C. Lewis,et al.  Correlation of SMNt and SMNc gene copy number with age of onset and survival in spinal muscular atrophy , 1998, European Journal of Human Genetics.

[14]  K. Davies,et al.  Maternal mosaicism for a second mutational event in a type I spinal muscular atrophy family. , 1998, American journal of human genetics.

[15]  Daniel L. Koller,et al.  Heterogeneity in hereditary pancreatitis. , 1998, American journal of medical genetics.

[16]  B. Wirth,et al.  De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling. , 1997, American journal of human genetics.

[17]  J. Mendell,et al.  Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. , 1997, American journal of human genetics.

[18]  M. Gorry,et al.  Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene , 1996, Nature Genetics.

[19]  K. Devriendt,et al.  Unusual molecular findings in autosomal recessive spinal muscular atrophy. , 1996, Journal of medical genetics.

[20]  E. Velasco,et al.  Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype. , 1996, Human molecular genetics.

[21]  A. Munnich,et al.  A frame–shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients , 1995, Nature Genetics.

[22]  B. Dallapiccola,et al.  Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients. , 1995, Biochemical and biophysical research communications.

[23]  B. Wirth,et al.  Allelic association and deletions in autosomal recessive proximal spinal muscular atrophy: association of marker genotype with disease severity and candidate cDNAs. , 1995, Human molecular genetics.

[24]  J. Osinga,et al.  PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy , 1995, The Lancet.

[25]  T. Crawford,et al.  The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy , 1995, Cell.

[26]  J. Weissenbach,et al.  Identification and characterization of a spinal muscular atrophy-determining gene , 1995, Cell.

[27]  D. Le Paslier,et al.  De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. , 1994, Science.

[28]  J. Pearn,et al.  Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. , 1978, Journal of medical genetics.

[29]  J. Pearn.  The Gene Frequency of Acute Werdnig-Hoffmann Disease (SMA Type 1). A Total Population Survey in North-East England , 1973, Journal of medical genetics.

[30]  M. Schwartz,et al.  Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy. , 1997, Human molecular genetics.

[31]  D. Bartelt,et al.  Human pancreatic secretory trypsin inhibitor. , 1976, Methods in enzymology.