LIPIN 2

Alternative Names

  • LPIN2

Associated Diseases

Majeed Syndrome
Back to search Result
OMIM Number

605519

Gene Map Locus
18p

Description

LIPIN 2 gene codes for a protein that belongs to a family of nuclear proteins. Three closely related members of the Lipin family, Lipin-1, Lipin-2, and Lipin-3 have been identified in both mouse and human. Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. It is identified that this gene is the only gene known to be associated with Majeed syndrome, probably playing a role in the regulation of the innate immune response.

Molecular Genetics

LIPIN 2 gene is located on the short arm of chromosome 18 and spans approximately 95 kb of genomic DNA with a coding sequence consisting of 20 exons. Exon 1 and the majority of exon 20 are non-coding (5' and 3' untranslated regions). The protein product of this gene is expressed in almost all tissues and comprises 896 amino acids and has a lipin domain and a SMP2 domain.

To date, three mutations have been identified in the LPIN2 in the three unrelated Arabic families affected with Majeed syndrome. Two of the three identified mutations are deleterious: one is a frameshift resulting from a 2-bp deletion and the other is a splice site mutation. The third mutation is a missense mutation that changes a highly evolutionary conserved serine with a leucine.

Epidemiology in the Arab World

View Map

Other Reports

Bahrain

Al-Mosawi et al. (2007) reported a unique mutation in LPIN2 in a consanguineous family with Majeed syndrome. The patient, a 3-year-old Arab girl, had hepatosplenomegaly and anemia as a neonate. At age 15 months, she developed recurrent episodes of fever and multifocal osteomyelitis. In addition, bone marrow aspiration demonstrated significant dyserythropoiesis, suggesting Majeed syndrome. Al-Mosawi et al. (2007) sequenced the coding region and splice sites of LPIN2 in the patient and her unaffected mother and detected a homozygous single-basepair change in the donor splice site of exon 17 (c.2327+1G-C) in the patient; her mother was heterozygous at this site. This splice site mutation is predicted to produce an R776S change followed by 65 amino acids prior to encountering a stop codon in intron 17. Al-Mosawi et al. (2007) did not find the R776S change in 734 ethnically controlled chromosomes or in a cohort of DNA samples from unaffected individuals of various ethnicities. Based on these data, Al-Mosawi et al. (2007) found that the allele frequency of the R776S change fulfills the definition of a mutation (<1%). Al-Mosawi et al. (2007) concluded that these data confirm the role of LPIN2 mutations in the etiology of Majeed syndrome.

Jordan

Ferguson et al. (2005) carried out a molecular study on two consanguineous Jordanian families with Majeed syndrome to map, identify, and characterize the causal gene and to speculate on its function and role in skin and bone inflammation. The first family had four affected individuals from two sibships and the second family had two affected siblings. Homozygosity mapping and parametric linkage analysis were employed for the localization of the gene responsible for Majeed syndrome. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Direct sequencing of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. The four affected individuals in the first family were found to be homozygous for a 2201C-T transition in exon 17 of the LPIN2 gene, resulting in a ser734-to-leu (S734L) substitution. The mutation was not found in 2,300 unrelated (CEPH) chromosomes, but it had a frequency of 0.005 (4 heterozygotes in 734 chromosomes) in 367 unrelated, ethnically matched Jordanian controls, leading to suggest that this mutation could be more prevalent in the Jordanian population due to a founder effect. The two affected individuals in the second family were found to be homozygous for a 2-bp deletion (540delAT) in exon 4 of the LPIN2 gene. This frame shift changes the amino acid in position 180 from threonine to praline to be followed by a stop codon in position 181. The mutation was not found in 2,300 unrelated (CEPH) chromosomes, or in 367 unrelated, ethnically matched Jordanian controls. Ferguson et al. (2005) carried out also expression studies and found that LPIN2 gene is expressed in al most all tissues.

© CAGS 2024. All rights reserved.