Mental Retardation, X-Linked 92

Clinical Features

Lugtenberg et al. (2006) studied a family in which 6 males in 3 generations had moderate to severe nonsyndromic mental retardation in an X-linked pattern of inheritance (XLMR). The 17-year-old proband had an IQ of 45. His mother had normal intelligence. He was the second son of unrelated parents and had 1 affected brother, 3 healthy sisters, and 1 carrier sister with borderline intelligence.

Mapping

The family reported by Lugtenberg et al. (2006) segregating X-linked mental retardation had previously been studied (family T40) by Raynaud et al. (2000), who found evidence of linkage of mental retardation to Xp11.3.

History

In a family in which 6 males in 3 generations had moderate to severe nonsyndromic mental retardation in a pattern consistent with X-linked recessive inheritance, Lugtenberg et al. (2006) identified a 352G-T transversion in exon 6 of ZNF674 cDNA, predicted to result in a glu118-to-ter (E118X; 300573.0001) truncated protein containing the Kruppel-associated box domains but lacking the zinc finger domains, which are crucial for DNA binding. The mutation was not found in 349 control X chromosomes.

Based on the finding of E118X and other truncating variants in ZNF674 in normal males in the NHLBI Exome Variant Server, and deletion of the ZNF674 gene in individuals without cognitive impairment (Delphin et al., 2012), Piton et al. (2013) found the implication of ZNF674 in XLMR to be unsupported.