(last modified September 30, 2006)
Weiler et al. mapped a locus for Limb-Girdle muscular dystrophy in Manitoba Hutterites (MIM-number 254110) to human chromosome region 9q31-q33, distal to the locus for Fukuyama congenital muscular dystrophy (FCMD). The locus was designated LGMD type 2H. Linkage was established with D9S302, LOD-score of 5.99 at recombination fraction 0.03. Highest LOD-score (7.61) was observed with D9S934. The gene most probably resides in a 300-kb region between D9S302 and D9S934.
The human tripartite motif-containing protein 32 gene (Gene Symbol TRIM32, alias TAT-interactive protien [72-kDa], zinc-finger protein HT2A) localizes to human chromosome 9q33.1. The gene contains two major exons. A thrid exon, designated 1b (see below) - located between exons 1 and 2, is a rare alternatively spliced exon.
|Exon||Exon size (in bp)||Intron size (in kb)||5' cDNA position||Splice after||Remarks|
|1b||61||230||-142||-||alternatively spliced exon, present in some rare transcripts|
|2||3089||-||-81||-||contains 5'UTR (81 bp), entire coding region and the 3'UTR|
Exon: numbering of exons and intron/exon boundaries are according to the genome sequence in relation to the cDNA Reference Sequence. Exon size: size of exon indicated in basepairs. Intron size: size of intron indicated in basepairs. 5' cDNA position: first base of the exon (in relation to the cDNA Reference Sequence. Splice after: splicing occurs in between of two coding triplets (0), after the first (1) or the second (2) base of a triplet or (-) in the UTR regions. Remarks: 5'UTR = 5' untranslated region, 3'UTR = 3' untranslated region.
LocusLink 22954 RefSeq: NM_012210
The TRIM32 mRNA, as detected on Northern blot, measures 3.3 kb. In addition, a weaker 2.5 kb transcript is also present. This size difference probably derives from the use of two polyA-addition sites, the minor site located 0.7 kb 5' of the site used by the majority of transcripts (dbEST, cDNA Reference Sequence). Some rare transcripts (e.g. BU176529 and BE778514) contain an alternatively spliced exon, designated exon 1b.
Human .. The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes.
Limb-Girdle muscular dystrophy type 2H (OMIM
LGMD-2H is a mild form of autosomal recessive Limb-Girdle muscular dystrophy described first in Manitoba Hutterites (Shokeir MHK, Clin.Genet. 9: 197). It maps to human chromosome region 9q31-q33, distal to the locus for Fukuyama congenital muscular dystrophy (FCMD) (Weiler et al.).
Frosk et al. (2002) decribe the identification of a homozygous change in the TRIM32 gene (1459G>A, Asp487Asn) in 35 American Hutterite families. Later, at the 2002 ASHG-meeting (abstract 2153, Am.J.Hum.Genet. 71: S537), Frosk et al. report that this homozygous change was found in 41 different LGMD-2H patients from their Hutterite families (Schmiedeleut). In addition they show that changes in either TRIM32 or FKRP (LGMD-2I, 19 patients) are responsible for all cases of LGMD2 in the Hutterite families they study.
Bardet-Biedl syndrome (BBS11, OMIM
Using homozygosity mapping in a small consanguineous Israelian Bedouin family Chiang et al. (2006) identified a likely pathogenic mutation in the TRIM32 gene (c.388C>T [p.Pro130Ser]). The authors used functional analysis in zebra fish and expression correlation analyses with other BBS genes in an expression quantitative trait loci data set to demonstrate that TRIM32 is the affected BBS gene.
|Amplified||Length||Reference||forward primer||reverse primer||Name|
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.
|Amplified||Length||Reference||Forward primer||Reverse primer||Name|
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to.... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.
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