Heterogeneity in hereditary pancreatitis

Majed J. Dasouki, Joy Cogan, Marshall L. Summar, Wallace Neblitt, Tatiana Foroud, Dan Koller, John A. Phillips

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ~25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic 'at-risk' relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalAmerican Journal of Medical Genetics
Volume77
Issue number1
DOIs
StatePublished - Apr 28 1998

Fingerprint

Trypsinogen
Mutation
Chronic Pancreatitis
Radiation Hybrid Mapping
Genes
Dinucleotide Repeats
Lod Score
Genetic Counseling
Hereditary pancreatitis
Histidine
Arginine
Exons
Chromosomes

Keywords

  • Centiray
  • Endoscopic retrograde cholangiopancreatography
  • Expressed tagged sequence
  • Hereditary pancreatitis
  • Logarithm of odds
  • Polymerase chain reaction
  • T-cell receptor β polypeptide
  • Theta (recombination fraction)

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Heterogeneity in hereditary pancreatitis. / Dasouki, Majed J.; Cogan, Joy; Summar, Marshall L.; Neblitt, Wallace; Foroud, Tatiana; Koller, Dan; Phillips, John A.

In: American Journal of Medical Genetics, Vol. 77, No. 1, 28.04.1998, p. 47-53.

Research output: Contribution to journalArticle

Dasouki, MJ, Cogan, J, Summar, ML, Neblitt, W, Foroud, T, Koller, D & Phillips, JA 1998, 'Heterogeneity in hereditary pancreatitis', American Journal of Medical Genetics, vol. 77, no. 1, pp. 47-53. https://doi.org/10.1002/(SICI)1096-8628(19980428)77:1<47::AID-AJMG11>3.0.CO;2-O
Dasouki, Majed J. ; Cogan, Joy ; Summar, Marshall L. ; Neblitt, Wallace ; Foroud, Tatiana ; Koller, Dan ; Phillips, John A. / Heterogeneity in hereditary pancreatitis. In: American Journal of Medical Genetics. 1998 ; Vol. 77, No. 1. pp. 47-53.
@article{c4ebff31cb2a4f0da1fa81358acd3d01,
title = "Heterogeneity in hereditary pancreatitis",
abstract = "Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ~25{\%} of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic 'at-risk' relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.",
keywords = "Centiray, Endoscopic retrograde cholangiopancreatography, Expressed tagged sequence, Hereditary pancreatitis, Logarithm of odds, Polymerase chain reaction, T-cell receptor β polypeptide, Theta (recombination fraction)",
author = "Dasouki, {Majed J.} and Joy Cogan and Summar, {Marshall L.} and Wallace Neblitt and Tatiana Foroud and Dan Koller and Phillips, {John A.}",
year = "1998",
month = "4",
day = "28",
doi = "10.1002/(SICI)1096-8628(19980428)77:1<47::AID-AJMG11>3.0.CO;2-O",
language = "English",
volume = "77",
pages = "47--53",
journal = "American Journal of Medical Genetics, Part C: Seminars in Medical Genetics",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Heterogeneity in hereditary pancreatitis

AU - Dasouki, Majed J.

AU - Cogan, Joy

AU - Summar, Marshall L.

AU - Neblitt, Wallace

AU - Foroud, Tatiana

AU - Koller, Dan

AU - Phillips, John A.

PY - 1998/4/28

Y1 - 1998/4/28

N2 - Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ~25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic 'at-risk' relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.

AB - Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ~25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic 'at-risk' relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.

KW - Centiray

KW - Endoscopic retrograde cholangiopancreatography

KW - Expressed tagged sequence

KW - Hereditary pancreatitis

KW - Logarithm of odds

KW - Polymerase chain reaction

KW - T-cell receptor β polypeptide

KW - Theta (recombination fraction)

UR - http://www.scopus.com/inward/record.url?scp=0032574682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032574682&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-8628(19980428)77:1<47::AID-AJMG11>3.0.CO;2-O

DO - 10.1002/(SICI)1096-8628(19980428)77:1<47::AID-AJMG11>3.0.CO;2-O

M3 - Article

C2 - 9557894

AN - SCOPUS:0032574682

VL - 77

SP - 47

EP - 53

JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

SN - 1552-4825

IS - 1

ER -