Mental Retardation, X-Linked 97

A number sign (#) is used with this entry because of evidence that this form of nonsyndromic X-linked mental retardation (MRX97) is caused by hemizygous mutation in the ZNF711 gene (314990) on chromosome Xq21.

Clinical Features

Yntema et al. (1999) reported a family (MRX65) in which 6 males in 3 generations had mild to moderate intellectual disability with speech delay. Four patients were obese. Van der Werf et al. (2017) provided follow-up of this family, noting that dysmorphic features included a broad face and prominent forehead. Van der Werf et al. (2017) reported another 4-generation family in which 5 males had mild to moderate intellectual disability, most often with motor delay and poor speech. Two had autistic features. Variable dysmorphic features included long face, synophrys, and relatively large ears.

Tarpey et al. (2009) identified 2 families with X-linked mental retardation and mutations in the ZNF711 gene. Mental retardation was moderate without consistent additional distinctive features. One affected individual did not carry a ZNF711 mutation.

Inheritance

The transmission pattern of MRX97 in the families reported by van der Werf et al. (2017) was consistent with X-linked recessive inheritance.

Molecular Genetics

Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. They identified 2 truncating mutations in the ZNF711 gene in 2 unrelated families.

In affected males from 2 unrelated families with MRX97, van der Werf et al. (2017) identified hemizygous mutations in the ZNF711 gene (314990.0003 and 314990.0004). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the families. One of the families had previously been reported by Yntema et al. (1999). Patient cells showed differential expression of several genes known to be expressed in the brain compared to controls, consistent with the putative function of ZNF711 as a transcription factor.