Zinc finger 81 (ZNF81) mutations associated with X-linked mental retardation

Kleefstra, Tjitske; Yntema, Helger G.; Oudakker, Astrid R.; Banning, Martijn J.G.; Kalscheuer, Vera M.; Chelly, Jamel; Moraine, Claude; Ropers, Hans‐Hilger; Fryns, J P; Janssen, Irene M.; Sistermans, Erik A.; Nillesen, W.; Vries, L.B.A. de; Hamel, B.C.J.; Bokhoven, Hans van

doi:10.1136/jmg.2003.016972

Cited by 63 publications

(47 citation statements)

References 23 publications

(29 reference statements)

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“…KRAB-domain zinc finger proteins are found in transcription regulatory complexes, which are directed to the regulatory elements of target genes through the C2H2 zinc finger domains that recognize specific DNA binding sites. Moreover, several human zinc finger genes have been associated with MR: ZNF41 (MIM 314995), ZNF81 (MIM 314998) and ZNF674 (MIM 300573) with X-linked MR [39][40][41] and ZNF385B (MIM 612344) with the 2q31.2 deletion syndrome. 41 Therefore, haploinsufficiency of ZNF778 might also, or exclusively, be involved in the phenotype observed in the reported patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

et al. 2009

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The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.

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Section: Discussionmentioning

confidence: 99%

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

et al. 2009

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“…Zinc finger protein 706 (ZNF706) has a sexspecific gene expression pattern (22) and is up-regulated in larynx tumors (23). Zinc finger protein 81 (ZNF81) is one of the three Xchromosome ZNF genes associated with nonsyndromic X-linked mental retardation (24). Histone H4 transcription factor (HINFP, also known as zinc finger protein 743, ZNF743) encodes a ZNF protein that interacts with methyl-CpG-binding protein 2 (MBD2) and is involved in transcriptional and epigenetic regulation (25).…”

mentioning

confidence: 99%

Widespread establishment and regulatory impact of Alu exons in human genes

Shen¹,

Lin²,

Cai

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

123

113

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The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements. However, identifying Alu exons that have acquired genuine biological functions remains a major challenge. We investigated the creation and establishment of Alu exons in human genes, using transcriptome profiles of human tissues generated by high-throughput RNA sequencing (RNA-Seq) combined with extensive RT-PCR analysis. More than 25% of Alu exons analyzed by RNASeq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes. Genes encoding zinc finger transcription factors have significantly higher levels of Alu exonization. Importantly, Alu exons with high splicing activities are strongly enriched in the 5′-UTR, and two-thirds (10/15) of 5′-UTR Alu exons tested by luciferase reporter assays significantly alter mRNA translational efficiency. Mutational analysis reveals the specific molecular mechanisms by which newly created 5′-UTR Alu exons modulate translational efficiency, such as the creation or elongation of upstream ORFs that repress the translation of the primary ORFs. This study presents genomic evidence that a major functional consequence of Alu exonization is the lineagespecific evolution of translational regulation. Moreover, the preferential creation and establishment of Alu exons in zinc finger genes suggest that Alu exonization may have globally affected the evolution of primate and human transcriptomes by regulating the protein production of master transcriptional regulators in specific lineages. transcriptome evolution | transposable element | alternative splicing | deep sequencing | uORF

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“…The ZNF674 gene is part of a zinc finger gene cluster in which two other zinc finger genes are known to be involved in XLMR: ZNF41 and ZNF81. 35,36 These data establish that there is a third KRAB/ZFP gene in this gene cluster that is involved in the development and/or maintenance of the human brain.…”

Section: High-resolution Arrays For X-linked Mental Retardationmentioning

confidence: 77%