#610153
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-49 (DFNB49) is caused by homozygous mutation in the TRIC gene (MARVELD2; 610572), which encodes tricellulin, on chromosome 5q13.
Autosomal recessive deafness-49 (DFNB49) is characterized by prelingual profound sensorineural hearing loss at all frequencies (Riazuddin et al., 2006 and Chishti et al., 2008).
Ramzan et al. (2005) reported 2 large consanguineous Pakistani families (PKDF041 and PKDF141) with autosomal recessive congenital profound sensorineural hearing loss of all frequencies. Genomewide linkage analysis followed by fine mapping of both families showed linkage to a candidate disease locus, termed DFNB49, on chromosome 5q12.3-q14.1 (maximum 2-point lod scores of 4.44 and 5.94 at D5S2055 and D5S424 in the 2 families, respectively). Haplotype analysis delineated an 11-cM interval flanked by D5S647 and D5S1501. Direct sequencing excluded mutations in coding regions of the SLC30A5 (607819) and SLC12A2 (600840) genes. One of the families (PKDF041) was later found to carry a homozygous mutation in the PPIP5K2 gene (611648.0001), consistent with a diagnosis of DFNB100 (618422).
Riazuddin et al. (2006) identified 6 additional DFNB49 families and refined the critical disease interval to 2.4 Mb.
In affected members of 6 families with DFNB49, Riazuddin et al. (2006) identified homozygous mutations in the TRIC gene to be the cause of the disorder. Four families were homozygous for the same disease haplotype and carried the same mutation located in the splice donor site of exon 4 (610572.0003). Two families segregated a deletion of this same splice donor site (610572.0002), and 1 family segregated a mutation in the splice acceptor site of exon 4 (610572.0001). Affected members of the remaining family carried a nonsense mutation in exon 5 (610572.0004). All of these mutations resulted in proteins that lacked the ability to bind to the scaffolding protein ZO1 (601009) because of the loss of the conserved C-terminal occludin-ELL domain.
In affected members of 3 consanguineous Pakistani kindreds with autosomal recessive nonsyndromic deafness, Chishti et al. (2008) identified 2 different homozygous mutations in the TRIC gene (610572.0003, 610572.0005), one of which had previously been reported. The authors estimated that the prevalence of autosomal recessive deafness due to TRIC mutations in Pakistani families is 1.06%.
Chishti, M. S., Bhatti, A., Tamim, S., Lee, K., McDonald, M.-L., Leal, S. M., Ahmad, W. Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families. J. Hum. Genet. 53: 101-105, 2008. [PubMed: 18084694, images, related citations] [Full Text]
Ramzan, K., Shaikh, R. S., Ahmad, J., Khan, S. N., Riazuddin, S., Ahmed, Z. M., Friedman, T. B., Wilcox, E. R., Riazuddin, S. A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Hum. Genet. 116: 17-22, 2005. [PubMed: 15538632, related citations] [Full Text]
Riazuddin, S., Ahmed, Z. M., Fanning, A. S., Lagziel, A., Kitajiri, S., Ramzan, K., Khan, S. N., Chattaraj, P., Friedman, P. L., Anderson, J. M., Belyantseva, I. A., Forge, A., Riazuddin, S., Friedman, T. B. Tricellulin is a tight-junction protein necessary for hearing. Am. J. Hum. Genet. 79: 1040-1051, 2006. [PubMed: 17186462, images, related citations] [Full Text]
ORPHA: 90636; DO: 0110506;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
5q13.2 | Deafness, autosomal recessive 49 | 610153 | Autosomal recessive | 3 | MARVELD2 | 610572 |
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-49 (DFNB49) is caused by homozygous mutation in the TRIC gene (MARVELD2; 610572), which encodes tricellulin, on chromosome 5q13.
Autosomal recessive deafness-49 (DFNB49) is characterized by prelingual profound sensorineural hearing loss at all frequencies (Riazuddin et al., 2006 and Chishti et al., 2008).
Ramzan et al. (2005) reported 2 large consanguineous Pakistani families (PKDF041 and PKDF141) with autosomal recessive congenital profound sensorineural hearing loss of all frequencies. Genomewide linkage analysis followed by fine mapping of both families showed linkage to a candidate disease locus, termed DFNB49, on chromosome 5q12.3-q14.1 (maximum 2-point lod scores of 4.44 and 5.94 at D5S2055 and D5S424 in the 2 families, respectively). Haplotype analysis delineated an 11-cM interval flanked by D5S647 and D5S1501. Direct sequencing excluded mutations in coding regions of the SLC30A5 (607819) and SLC12A2 (600840) genes. One of the families (PKDF041) was later found to carry a homozygous mutation in the PPIP5K2 gene (611648.0001), consistent with a diagnosis of DFNB100 (618422).
Riazuddin et al. (2006) identified 6 additional DFNB49 families and refined the critical disease interval to 2.4 Mb.
In affected members of 6 families with DFNB49, Riazuddin et al. (2006) identified homozygous mutations in the TRIC gene to be the cause of the disorder. Four families were homozygous for the same disease haplotype and carried the same mutation located in the splice donor site of exon 4 (610572.0003). Two families segregated a deletion of this same splice donor site (610572.0002), and 1 family segregated a mutation in the splice acceptor site of exon 4 (610572.0001). Affected members of the remaining family carried a nonsense mutation in exon 5 (610572.0004). All of these mutations resulted in proteins that lacked the ability to bind to the scaffolding protein ZO1 (601009) because of the loss of the conserved C-terminal occludin-ELL domain.
In affected members of 3 consanguineous Pakistani kindreds with autosomal recessive nonsyndromic deafness, Chishti et al. (2008) identified 2 different homozygous mutations in the TRIC gene (610572.0003, 610572.0005), one of which had previously been reported. The authors estimated that the prevalence of autosomal recessive deafness due to TRIC mutations in Pakistani families is 1.06%.
Chishti, M. S., Bhatti, A., Tamim, S., Lee, K., McDonald, M.-L., Leal, S. M., Ahmad, W. Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families. J. Hum. Genet. 53: 101-105, 2008. [PubMed: 18084694] [Full Text: https://doi.org/10.1007/s10038-007-0209-3]
Ramzan, K., Shaikh, R. S., Ahmad, J., Khan, S. N., Riazuddin, S., Ahmed, Z. M., Friedman, T. B., Wilcox, E. R., Riazuddin, S. A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Hum. Genet. 116: 17-22, 2005. [PubMed: 15538632] [Full Text: https://doi.org/10.1007/s00439-004-1205-8]
Riazuddin, S., Ahmed, Z. M., Fanning, A. S., Lagziel, A., Kitajiri, S., Ramzan, K., Khan, S. N., Chattaraj, P., Friedman, P. L., Anderson, J. M., Belyantseva, I. A., Forge, A., Riazuddin, S., Friedman, T. B. Tricellulin is a tight-junction protein necessary for hearing. Am. J. Hum. Genet. 79: 1040-1051, 2006. [PubMed: 17186462] [Full Text: https://doi.org/10.1086/510022]
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