Chromosome Xp11.3 Deletion Syndrome

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

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Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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A number sign (#) is used with this entry because it represents a contiguous gene syndrome involving deletion of chromosome Xp11.3, including the RP2 gene (300757).

Clinical Features

Aldred et al. (1994) reported a family in which 5 males in 3 generations had mild to moderate mental retardation associated with severe, early-onset retinitis pigmentosa. Some affected males also had microcephaly. Although some obligate female carriers showed visual impairment, all were intellectually normal.

Mapping

Linkage analysis of the family reported by Aldred et al. (1994) identified a candidate locus on Xp21-q21. Multipoint analysis placed the maximum likelihood region to Xp11.4-p11.23, although the lod score was not significant.

Molecular Genetics

In a follow-up of the family reported by Aldred et al. (1994), Zhang et al. (2006) found that affected individuals had a 1.27-Mb deletion on Xp11, including the 5-prime end of the RP2 gene, the SLC9A7 (300368), ZNF673 (300585), and CHST7 (300375) genes, and 2 genes encoding microRNAs (MIRN221, 300568; MIRN222, 300569). Zhang et al. (2006) concluded that the disorder in this family is a contiguous gene deletion syndrome and that absence of the RP2 gene accounts for retinal degeneration. One or more of the other deleted genes is likely responsible for mental retardation.

Lugtenberg et al. (2006) identified a patient with learning disabilities, retinal dystrophy, and short stature whose family history was suggestive of an X-linked contiguous gene syndrome. By array-based comparative genomic hybridization with full-coverage X-chromosomal BAC arrays, they found a deletion of approximately 1 Mb in Xp11.3. The deletion was found to harbor several candidate genes for X-linked mental retardation (XLMR), which were screened in probands from 28 families with nonsyndromic XLMR that showed linkage to Xp11.3. In 1 family, Lugtenberg et al. (2006) found a nonsense mutation (E118X; 300573.0001) in the coding sequence of the ZNF674 gene.

In 2 unrelated families in which males were affected with retinal dystrophy but had normal intellectual development, Delphin et al. (2012) identified deletions on chromosome Xp11.3 that involved the RP2 gene as well as the ZNF674 gene. The authors concluded that their findings cast doubt on the responsibility of ZNF674 deletions in mental retardation associated with X-linked retinal dystrophy.