Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

P. J. Ferguson, S. Chen, M. K. Tayeh, L. Ochoa, S. M. Leal, A. Pelet, A. Munnich, S. Lyonnet, H. A. Majeed, Hatem El-Shanti

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

Original languageEnglish
Pages (from-to)551-557
Number of pages7
JournalJournal of Medical Genetics
Volume42
Issue number7
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

Fingerprint

Mutation
Osteitis
Genes
Sweet Syndrome
Skin
Chromosome Mapping
Majeed syndrome
Psoriasis
Computer Simulation
Anemia
Fever
Chromosomes
Inflammation
Phenotype
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). / Ferguson, P. J.; Chen, S.; Tayeh, M. K.; Ochoa, L.; Leal, S. M.; Pelet, A.; Munnich, A.; Lyonnet, S.; Majeed, H. A.; El-Shanti, Hatem.

In: Journal of Medical Genetics, Vol. 42, No. 7, 07.2005, p. 551-557.

Research output: Contribution to journalArticle

Ferguson, P. J. ; Chen, S. ; Tayeh, M. K. ; Ochoa, L. ; Leal, S. M. ; Pelet, A. ; Munnich, A. ; Lyonnet, S. ; Majeed, H. A. ; El-Shanti, Hatem. / Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). In: Journal of Medical Genetics. 2005 ; Vol. 42, No. 7. pp. 551-557.
@article{8361c58d5f2e46dfbfddedc0f5915b4e,
title = "Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)",
abstract = "Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.",
author = "Ferguson, {P. J.} and S. Chen and Tayeh, {M. K.} and L. Ochoa and Leal, {S. M.} and A. Pelet and A. Munnich and S. Lyonnet and Majeed, {H. A.} and Hatem El-Shanti",
year = "2005",
month = "7",
doi = "10.1136/jmg.2005.030759",
language = "English",
volume = "42",
pages = "551--557",
journal = "Shock",
issn = "1073-2322",
publisher = "BMJ Publishing Group",
number = "7",

}

TY - JOUR

T1 - Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

AU - Ferguson, P. J.

AU - Chen, S.

AU - Tayeh, M. K.

AU - Ochoa, L.

AU - Leal, S. M.

AU - Pelet, A.

AU - Munnich, A.

AU - Lyonnet, S.

AU - Majeed, H. A.

AU - El-Shanti, Hatem

PY - 2005/7

Y1 - 2005/7

N2 - Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

AB - Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

UR - http://www.scopus.com/inward/record.url?scp=22244469461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22244469461&partnerID=8YFLogxK

U2 - 10.1136/jmg.2005.030759

DO - 10.1136/jmg.2005.030759

M3 - Article

C2 - 15994876

AN - SCOPUS:22244469461

VL - 42

SP - 551

EP - 557

JO - Shock

JF - Shock

SN - 1073-2322

IS - 7

ER -