Mutation analyses of North American APS-1 patients

Maarit Heino, Hamish S. Scott, Qiaoyi Chen, Pärt Peterson, Ulla Mäenpää, Marie Pierre Papasavvas, Laureane Mittaz, Christine Barras, Colette Rossier, George P. Chrousos, Constantine A. Stratakis, Kentaro Nagamine, Jun Kudo, Nobuyoshi Shimizu, Noel Maclaren, Stylianos E. Antonarakis, Kai Krohn

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS- 1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalHuman Mutation
Volume13
Issue number1
DOIs
Publication statusPublished - 1999

Fingerprint

Mutation
Regulator Genes
Haplotypes
Autoimmune Polyendocrinopathies
Alleles
Endocrine Glands
Genetic Association Studies
North America
Introns
Autoimmune Diseases
Disease Progression
Exons
Population
Genes

Keywords

  • Autoimmunity
  • Chromosome 21
  • Polyendocrinopathies

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Heino, M., Scott, H. S., Chen, Q., Peterson, P., Mäenpää, U., Papasavvas, M. P., ... Krohn, K. (1999). Mutation analyses of North American APS-1 patients. Human Mutation, 13(1), 69-74. https://doi.org/10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6

Mutation analyses of North American APS-1 patients. / Heino, Maarit; Scott, Hamish S.; Chen, Qiaoyi; Peterson, Pärt; Mäenpää, Ulla; Papasavvas, Marie Pierre; Mittaz, Laureane; Barras, Christine; Rossier, Colette; Chrousos, George P.; Stratakis, Constantine A.; Nagamine, Kentaro; Kudo, Jun; Shimizu, Nobuyoshi; Maclaren, Noel; Antonarakis, Stylianos E.; Krohn, Kai.

In: Human Mutation, Vol. 13, No. 1, 1999, p. 69-74.

Research output: Contribution to journalArticle

Heino, M, Scott, HS, Chen, Q, Peterson, P, Mäenpää, U, Papasavvas, MP, Mittaz, L, Barras, C, Rossier, C, Chrousos, GP, Stratakis, CA, Nagamine, K, Kudo, J, Shimizu, N, Maclaren, N, Antonarakis, SE & Krohn, K 1999, 'Mutation analyses of North American APS-1 patients', Human Mutation, vol. 13, no. 1, pp. 69-74. https://doi.org/10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6
Heino M, Scott HS, Chen Q, Peterson P, Mäenpää U, Papasavvas MP et al. Mutation analyses of North American APS-1 patients. Human Mutation. 1999;13(1):69-74. https://doi.org/10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6
Heino, Maarit ; Scott, Hamish S. ; Chen, Qiaoyi ; Peterson, Pärt ; Mäenpää, Ulla ; Papasavvas, Marie Pierre ; Mittaz, Laureane ; Barras, Christine ; Rossier, Colette ; Chrousos, George P. ; Stratakis, Constantine A. ; Nagamine, Kentaro ; Kudo, Jun ; Shimizu, Nobuyoshi ; Maclaren, Noel ; Antonarakis, Stylianos E. ; Krohn, Kai. / Mutation analyses of North American APS-1 patients. In: Human Mutation. 1999 ; Vol. 13, No. 1. pp. 69-74.
@article{793ac8a2d9dd420ebd64b45504e0abd7,
title = "Mutation analyses of North American APS-1 patients",
abstract = "Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS- 1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.",
keywords = "Autoimmunity, Chromosome 21, Polyendocrinopathies",
author = "Maarit Heino and Scott, {Hamish S.} and Qiaoyi Chen and P{\"a}rt Peterson and Ulla M{\"a}enp{\"a}{\"a} and Papasavvas, {Marie Pierre} and Laureane Mittaz and Christine Barras and Colette Rossier and Chrousos, {George P.} and Stratakis, {Constantine A.} and Kentaro Nagamine and Jun Kudo and Nobuyoshi Shimizu and Noel Maclaren and Antonarakis, {Stylianos E.} and Kai Krohn",
year = "1999",
doi = "10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6",
language = "English",
volume = "13",
pages = "69--74",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Mutation analyses of North American APS-1 patients

AU - Heino, Maarit

AU - Scott, Hamish S.

AU - Chen, Qiaoyi

AU - Peterson, Pärt

AU - Mäenpää, Ulla

AU - Papasavvas, Marie Pierre

AU - Mittaz, Laureane

AU - Barras, Christine

AU - Rossier, Colette

AU - Chrousos, George P.

AU - Stratakis, Constantine A.

AU - Nagamine, Kentaro

AU - Kudo, Jun

AU - Shimizu, Nobuyoshi

AU - Maclaren, Noel

AU - Antonarakis, Stylianos E.

AU - Krohn, Kai

PY - 1999

Y1 - 1999

N2 - Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS- 1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.

AB - Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS- 1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.

KW - Autoimmunity

KW - Chromosome 21

KW - Polyendocrinopathies

UR - http://www.scopus.com/inward/record.url?scp=0032902386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032902386&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6

DO - 10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6

M3 - Article

C2 - 9888391

AN - SCOPUS:0032902386

VL - 13

SP - 69

EP - 74

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 1

ER -