HGNC Approved Gene Symbol: LPIN2
SNOMEDCT: 703540008; ICD10CM: M04.8;
Cytogenetic location: 18p11.31 Genomic coordinates (GRCh38) : 18:2,916,994-3,013,144 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 18p11.31 | Majeed syndrome | 609628 | 3 |
Mice carrying mutations in the fatty liver dystrophy (fld) gene have features of human lipodystrophy (Reue et al., 2000). In the human, lipodystrophy is a heterogeneous group of disorders characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. Through positional cloning, Peterfy et al. (2001) isolated the gene responsible for fatty liver dystrophy in mice and characterized 2 independent mutant alleles of the fld gene. They designated the gene Lpin1 and named the novel nuclear protein which it encodes lipin. Through database searches, Peterfy et al. (2001) identified several mouse and human EST and genomic sequences with similarities to Lpin1. These included 2 Lpin1-related mouse genes (Lpin2 and Lpin3) and 3 human homologs (LPIN1 (605518), LPIN2, and LPIN3 (605520)). LPIN2 is identical to the KIAA0249 gene identified by Nagase et al. (1996).
By PCR and Northern blot analysis, Ferguson et al. (2005) detected a 6-kb LPIN2 transcript in multiple human tissues including liver, lung, kidney, and placenta.
Ferguson et al. (2005) noted that the LPIN2 gene contains 20 exons spanning 95 kb.
Using sequence databases, Peterfy et al. (2001) mapped the human LPIN2 gene to 18p. They mapped the mouse gene to chromosome 17.
In 2 consanguineous Arab families with Majeed syndrome (MJDS; 609628), previously reported by Majeed et al. (1989, 2000, 2001), Ferguson et al. (2005) identified homozygosity for a missense mutation (S734L; 605519.0001) and a 2-bp deletion (605519.0002) in the LPIN2 gene, respectively.
In 4 affected members of 2 consanguineous sibships of a Jordanian Arab family with Majeed syndrome (MJDS; 609628), previously reported by Majeed et al. (1989, 2000), Ferguson et al. (2005) identified homozygosity 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.
In 2 affected sibs of a consanguineous Jordanian Arab family with Majeed syndrome (MJDS; 609628), previously reported by Majeed et al. (2001), Ferguson et al. (2005) identified homozygosity for a 2-bp deletion (540delAT) in exon 4 of the LPIN2 gene, resulting in a stop codon at position 181. The mutation was not found in 2,300 unrelated (CEPH) chromosomes, or in 367 unrelated, ethnically matched Jordanian controls.
Ferguson, P. J., Chen, S., Tayeh, M. K., Ochoa, L., Leal, S. M., Pelet, A., Munnich, A., Lyonnet, S., Majeed, H. A., El-Shanti, H. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J. Med. Genet. 42: 551-557, 2005. [PubMed: 15994876] [Full Text: https://doi.org/10.1136/jmg.2005.030759]
Majeed, H. A., Al-Tarawna, M., El-Shanti, H., Kamel, B., Al-Khalaileh, F. The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia: report of a new family and a review. Europ. J. Pediat. 160: 705-710, 2001. [PubMed: 11795677] [Full Text: https://doi.org/10.1007/s004310100799]
Majeed, H. A., El-Shanti, H., Al-Rimawa, H., Al-Masri, N. On mice and men: an autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia. (Letter) J. Pediat. 137: 441-442, 2000. [PubMed: 10969284] [Full Text: https://doi.org/10.1067/mpd.2000.107613]
Majeed, H. A., Kalaawi, M., Mohanty, D., Teebi, A. S., Tunjekar, M. F., Al-Gharbawy, F., Majeed, S. A., Al-Gazzar, A. H. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. J. Pediat. 115: 730-734, 1989. [PubMed: 2809904] [Full Text: https://doi.org/10.1016/s0022-3476(89)80650-x]
Nagase, T., Seki, N., Ishikawa, K., Ohira, M., Kawarabayasi, Y., Ohara, O., Tanaka, A., Kotani, H., Miyajima, N., Nomura, N. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 3: 321-329, 1996. [PubMed: 9039502] [Full Text: https://doi.org/10.1093/dnares/3.5.321]
Peterfy, M., Phan, J., Xu, P., Reue, K. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nature Genet. 27: 121-124, 2001. [PubMed: 11138012] [Full Text: https://doi.org/10.1038/83685]
Reue, K., Xu, P., Wang, X.-P., Slavin, B. G. Adipose tissue deficiency, glucose intolerance, and increased atherosclerosis result from mutation in the mouse fatty liver dystrophy (fld) gene. J. Lipid Res. 41: 1067-1076, 2000. [PubMed: 10884287]