Mental Retardation, X-Linked 88

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

IQSEC2, DLG3, GDI1, PAK3, ACSL4, ARX, MECP2, RPS6KA3, HCFC1, IL1RAPL1, TSPAN7, FTSJ1, ZNF41, DMD, CNKSR2, MID2, AGTR2, UPF3B, CXorf56, FRMPD4, ALG13, SLC9A7, RAB39B, PTCHD1, ZNF81, MED12, ZNF711, ARHGEF6, SYP, CLCN4, USP27X, USP9X, ABCG2, FRAXE, AFF2, STS, OPHN1, ALAS2, POU3F4, SERPINA4, RPS6KA6, THOC2, ANOS1, FMR1, ELK1

Drugs

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Clinical Features

Vervoort et al. (2002) reported 9 male patients with a mutation in the AGTR2 gene who had moderate to severe mental retardation. Five of the patients had seizures and, with the exception of 1 patient, they were not hypertensive. Two patients also showed autistic behavior.

Cytogenetics

Vervoort et al. (2002) analyzed a de novo balanced translocation 46,X,t(X;7)(q24;q22) in a female patient with moderate mental retardation. This patient had completely skewed X inactivation. They mapped the X-chromosome breakpoint and demonstrated by RT-PCR that the AGTR2 gene was silenced in this patient.

History

Vervoort et al. (2002) screened affected males from 33 families with possible X-linked MR but no definitive linkage data, and a large cohort of 552 unrelated male patients with MR of unknown cause but negative for the FMR1 expansion. Eight of the 590 unrelated male patients with MR were found to have sequence changes in the AGTR2 gene, including 1 frameshift (300034.0001) and 3 missense mutations (300034.0002-300034.0004). Five of 9 patients with AGTR2 mutations had seizures and, with the exception of 1 patient, they were not hypertensive. The mental retardation ranged from moderate to severe. Two patients also showed autistic behavior. Vervoort et al. (2002) concluded that there is a role for AGTR2 in brain development and cognitive function.

Bienvenu et al. (2003) performed mutation analysis of the AGTR2 gene in 15 large families with MR linked to Xq24, a panel of 101 clinically well-characterized small families with at least 2 affected boys with MR, and 244 sporadic cases of nonspecific MR. No deleterious mutations were found in any of the patients. A novel amino acid substitution was identified as a nonpathogenic rare genetic variant. These observations suggested that AGTR2 is rarely involved in nonspecific MR but could be involved in more specific forms.

Based on their occurrence in normal males, Piton et al. (2013) considered variants in the AGTR2 gene very unlikely to play a role in X-linked mental retardation.