#611090
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-12 (MRT12) is caused by homozygous mutation in the ST3GAL3 gene (606494) on chromosome 1p34.
Najmabadi et al. (2007) and Hu et al. (2011) reported 2 unrelated consanguineous Iranian families with nonsyndromic mildly to moderately impaired intellectual development.
Farajollahi et al. (2020) reported 2 first cousins (patients V.2 and V.4) from a consanguineous Iranian family with nonsyndromic severely impaired intellectual development. The patients, aged 31 and 27 years, had aggressive behavior, difficulty walking, loss of acquired skills, chronic lung disease, and a history of neonatal jaundice. Two other family members (sibs of patient V.4) had a history of similar clinical features, but were deceased and did not have molecular testing.
Najmabadi et al. (2007) reported a large consanguineous Iranian family in which 8 individuals had nonsyndromic mildly impaired intellectual development. Linkage analysis identified a candidate locus on chromosome 1p34-p33 with a maximum lod score of 7.2. Haplotype analysis delineated a 9.4-Mb candidate region between rs514262 and rs953070.
In affected members of 2 unrelated consanguineous Iranian families with MRT12, including the one reported by Najmabadi et al. (2007), Hu et al. (2011) used linkage analysis, chromosome sorting, and next-generation sequencing and identified 2 different homozygous mutations in the ST3GAL3 gene (A13D, 606494.0001 and D370Y, 606494.0002, respectively). Neither mutation affected the highly conserved sialyl motifs, but rather affected the N-terminal transmembrane domain and C-terminal catalytic domain, respectively. In vitro functional expression studies showed that the mutant proteins were mislocalized to the endoplasmic reticulum and that 1 (D370Y) had loss of catalytic activity. The findings demonstrated a link between the glycoprotein complex, sialyltransferase activity, and higher cognitive functioning.
In 2 first cousins with severely impaired intellectual development from a consanguineous Iranian family, Farajollahi et al. (2020) identified a homozygous missense mutation (T235M; 606494.0004). The mutation segregated with disease in the family. Molecular modeling predicted that the mutation might interfere with ligand binding and decrease protein stability.
Although Najmabadi et al. (2007) referred to this locus as 'MRT4,' that designation had already been used by Uyguner et al. (2007) to refer to a locus on chromosome 1p21.1-p13.3 (MRT4; 611107). Thus, the locus described here is referred to as MRT12.
Farajollahi, Z., Razmara, E., Heidari, E., Jafarinia, E., Garshasbi, M. A novel variant of ST3GAL3 causes non-syndromic autosomal recessive intellectual disability in Iranian patients. J. Gene Med. 22: e3253, 2020. Note: Electronic Article. [PubMed: 32666583, related citations] [Full Text]
Hu, H., Eggers, K., Chen, W., Garshasbi, M., Motazacker, M. M., Wrogemann, K., Kahrizi, K., Tzschach, A., Hosseini, M., Bahman, I., Hucho, T., Muhlenhoff, M., Gerardy-Schahn, R., Najmabadi, H., Ropers, H. H., Kuss, A. W. ST3GAL3 mutations impair the development of higher cognitive functions. Am. J. Hum. Genet. 89: 407-414, 2011. [PubMed: 21907012, images, related citations] [Full Text]
Najmabadi, H., Motazacker, M. M., Garshasbi, M., Kahrizi, K., Tzschach, A., Chen, W., Behjati, F., Hadavi, V., Nieh, S. E., Abedini, S. S., Vazifehmand, R., Firouzabadi, S. G., and 9 others. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Hum. Genet. 121: 43-48, 2007. [PubMed: 17120046, related citations] [Full Text]
Uyguner, O., Kayserili, H., Li, Y., Karaman, B., Nurnberg, G., Hennies, H. C., Becker, C., Nurnberg, P., Basaran, S., Apak, M. Y., Wollnik, B. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3. Clin. Genet. 71: 212-219, 2007. [PubMed: 17309643, related citations] [Full Text]
ORPHA: 88616; DO: 0081180;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
1p34.1 | Intellectual developmental disorder, autosomal recessive 12 | 611090 | Autosomal recessive | 3 | ST3GAL3 | 606494 |
A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-12 (MRT12) is caused by homozygous mutation in the ST3GAL3 gene (606494) on chromosome 1p34.
Najmabadi et al. (2007) and Hu et al. (2011) reported 2 unrelated consanguineous Iranian families with nonsyndromic mildly to moderately impaired intellectual development.
Farajollahi et al. (2020) reported 2 first cousins (patients V.2 and V.4) from a consanguineous Iranian family with nonsyndromic severely impaired intellectual development. The patients, aged 31 and 27 years, had aggressive behavior, difficulty walking, loss of acquired skills, chronic lung disease, and a history of neonatal jaundice. Two other family members (sibs of patient V.4) had a history of similar clinical features, but were deceased and did not have molecular testing.
Najmabadi et al. (2007) reported a large consanguineous Iranian family in which 8 individuals had nonsyndromic mildly impaired intellectual development. Linkage analysis identified a candidate locus on chromosome 1p34-p33 with a maximum lod score of 7.2. Haplotype analysis delineated a 9.4-Mb candidate region between rs514262 and rs953070.
In affected members of 2 unrelated consanguineous Iranian families with MRT12, including the one reported by Najmabadi et al. (2007), Hu et al. (2011) used linkage analysis, chromosome sorting, and next-generation sequencing and identified 2 different homozygous mutations in the ST3GAL3 gene (A13D, 606494.0001 and D370Y, 606494.0002, respectively). Neither mutation affected the highly conserved sialyl motifs, but rather affected the N-terminal transmembrane domain and C-terminal catalytic domain, respectively. In vitro functional expression studies showed that the mutant proteins were mislocalized to the endoplasmic reticulum and that 1 (D370Y) had loss of catalytic activity. The findings demonstrated a link between the glycoprotein complex, sialyltransferase activity, and higher cognitive functioning.
In 2 first cousins with severely impaired intellectual development from a consanguineous Iranian family, Farajollahi et al. (2020) identified a homozygous missense mutation (T235M; 606494.0004). The mutation segregated with disease in the family. Molecular modeling predicted that the mutation might interfere with ligand binding and decrease protein stability.
Although Najmabadi et al. (2007) referred to this locus as 'MRT4,' that designation had already been used by Uyguner et al. (2007) to refer to a locus on chromosome 1p21.1-p13.3 (MRT4; 611107). Thus, the locus described here is referred to as MRT12.
Farajollahi, Z., Razmara, E., Heidari, E., Jafarinia, E., Garshasbi, M. A novel variant of ST3GAL3 causes non-syndromic autosomal recessive intellectual disability in Iranian patients. J. Gene Med. 22: e3253, 2020. Note: Electronic Article. [PubMed: 32666583] [Full Text: https://doi.org/10.1002/jgm.3253]
Hu, H., Eggers, K., Chen, W., Garshasbi, M., Motazacker, M. M., Wrogemann, K., Kahrizi, K., Tzschach, A., Hosseini, M., Bahman, I., Hucho, T., Muhlenhoff, M., Gerardy-Schahn, R., Najmabadi, H., Ropers, H. H., Kuss, A. W. ST3GAL3 mutations impair the development of higher cognitive functions. Am. J. Hum. Genet. 89: 407-414, 2011. [PubMed: 21907012] [Full Text: https://doi.org/10.1016/j.ajhg.2011.08.008]
Najmabadi, H., Motazacker, M. M., Garshasbi, M., Kahrizi, K., Tzschach, A., Chen, W., Behjati, F., Hadavi, V., Nieh, S. E., Abedini, S. S., Vazifehmand, R., Firouzabadi, S. G., and 9 others. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Hum. Genet. 121: 43-48, 2007. [PubMed: 17120046] [Full Text: https://doi.org/10.1007/s00439-006-0292-0]
Uyguner, O., Kayserili, H., Li, Y., Karaman, B., Nurnberg, G., Hennies, H. C., Becker, C., Nurnberg, P., Basaran, S., Apak, M. Y., Wollnik, B. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3. Clin. Genet. 71: 212-219, 2007. [PubMed: 17309643] [Full Text: https://doi.org/10.1111/j.1399-0004.2007.00762.x]
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