Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on Chromosome 7q11.23

Purpose: To identify the relationship between specific genes and phenotypic features of Williams syndrome.Methods: Subjects were selected based on their deletion status determined by fluorescence in situ hybridization using a panel of 24 BACs and cosmids spanning the region commonly deleted and single gene analysis using Southern blotting. From the cohort of subjects, three had atypical deletions. Physical examinations and cognitive tests were administered to the three subjects and the results were compared to those from a cohort of typical WS subjects.Results: The molecular results indicate smaller deletions for each subject. In all three cases, typical Williams facies were absent and visual spatial abilities were above that of full deletion WS subjects, particularly in the qualitative aspects of visual spatial processing.Conclusions: Combining the molecular analysis with the cognitive results suggest that the genes GTF2IRD1 and GTF2I contribute to deficits on visual spatial functioning.

[1]  U. Francke,et al.  TBL2, a novel transducin family member in the WBS deletion: characterization of the complete sequence, genomic structure, transcriptional variants and the mouse ortholog , 1999, Cytogenetic and Genome Research.

[2]  C. Morris,et al.  A novel human gene, WSTF, is deleted in Williams syndrome. , 1998, Genomics.

[3]  K. Fujimoto,et al.  Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  L. Shaffer,et al.  Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin. , 1998, American journal of medical genetics.

[5]  U. Francke,et al.  A physical map, including a BAC/PAC clone contig, of the Williams-Beuren syndrome--deletion region at 7q11.23. , 2000, American journal of human genetics.

[6]  C A Morris,et al.  Natural history of Williams syndrome: physical characteristics. , 1988, The Journal of pediatrics.

[7]  C. Mervis,et al.  Visuospatial construction. , 1999, American journal of human genetics.

[8]  Ursula Bellugi,et al.  I. The Neurocognitive Profile of Williams Syndrome: A Complex Pattern of Strengths and Weaknesses , 2000, Journal of Cognitive Neuroscience.

[9]  K. Mikoshiba,et al.  Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2. , 1997, Genomics.

[10]  C. Disteche,et al.  Down syndrome phenotypes: the consequences of chromosomal imbalance. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[11]  lhealtlhy youin-g,et al.  Hospital for Sick Children , 1857, British medical journal.

[12]  P. Howlin,et al.  Cognitive functioning in adults with Williams syndrome. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[13]  Marleen Verhoye,et al.  Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice , 2002, Nature Genetics.

[14]  R. Nusse,et al.  A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. , 1997, Human molecular genetics.

[15]  E. Hardeman,et al.  Identification of a Novel Slow-Muscle-Fiber Enhancer Binding Protein, MusTRD1 , 2000, Molecular and Cellular Biology.

[16]  S. Warschausky,et al.  WISC-III index growth curve characteristics following traumatic brain injury. Wechsler Intelligence Scale for Children--Third Edition. , 1999, Journal of clinical and experimental neuropsychology.

[17]  W. Miller,et al.  Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome , 2000, Cytogenetic and Genome Research.

[18]  U. Francke,et al.  Identification of GTF2IRD1, a putative transcription factor within the Williams-Beuren syndrome deletion at 7q11.23 , 1999, Cytogenetic and Genome Research.

[19]  S. Scherer,et al.  Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. , 1996, Genomics.

[20]  W. F. Vonderhaar.  A COMPARATIVE STUDY OF PERFORMANCE SCALE IQ'S AND SUBTEST SCORES OF DEAF CHILDREN ON THE WECHSLER INTELLIGENCE SCALE FOR CHILDREN AND THE WECHSLER INTELLIGENCE SCALE FOR CHILDREN-REVISED , 1977 .

[21]  Ursula Bellugi,et al.  Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome , 1999, Trends in Neurosciences.

[22]  W. Reardon,et al.  Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis. , 1997, Human molecular genetics.

[23]  S. Scherer,et al.  Identification of a putative transcription factor gene (WBSCR11) that is commonly deleted in Williams-Beuren syndrome. , 1999, Genomics.

[24]  U. Francke,et al.  Identification of the WBSCR9 gene, encoding a novel transcriptional regulator, in the Williams-Beuren syndrome deletion at 7q11.23 , 1998, Cytogenetic and Genome Research.

[25]  S. Desiderio,et al.  BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. C. Valero,et al.  WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse ortholog , 2000, European Journal of Human Genetics.

[27]  C. Morris,et al.  A novel human gene FKBP6 is deleted in Williams syndrome. , 1998, Genomics.

[28]  S. Scherer,et al.  The BCL7 gene family: deletion of BCL7B in Williams syndrome. , 1998, Gene.

[29]  M. Noble,et al.  Assignment of the human and mouse LIM-kinase genes (LIMK1; Limk1) to chromosome bands 7q11.23 and 5G1, respectively, by in situ hybridization. , 1996, Cytogenetics and Cell Genetics.

[30]  J. Katahira,et al.  Clostridium perfringens Enterotoxin Utilizes Two Structurally Related Membrane Proteins as Functional Receptors in Vivo * , 1997, The Journal of Biological Chemistry.

[31]  Kazushi Fujimoto,et al.  Claudin-1 and -2: Novel Integral Membrane Proteins Localizing at Tight Junctions with No Sequence Similarity to Occludin , 1998, The Journal of cell biology.

[32]  G. Hickok,et al.  Hemispheric Organization of Local- and Global-Level Visuospatial Processes in Deaf Signers and Its Relation to Sign Language Aphasia , 1998, Brain and Language.

[33]  H. Himmelbauer,et al.  Localization of the human HIP1 gene close to the elastin (ELN) locus on 7q11.23. , 1997, Genomics.

[34]  I. T. Draper.  THE ASSESSMENT OF APHASIA AND RELATED DISORDERS , 1973 .

[35]  U. Francke,et al.  The gene for replication factor C subunit 2 (RFC2) is within the 7q11.23 Williams syndrome deletion. , 1996, American journal of human genetics.

[36]  U. Francke,et al.  Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. , 1996, American journal of human genetics.

[37]  X. Chen,et al.  Using fluorescence in situ hybridization (FISH) in genome mapping. , 1992, Trends in biotechnology.

[38]  U. Francke,et al.  A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. , 1998, Human molecular genetics.

[39]  I. L. Zimmerman,et al.  Clinical Interpretation of the Wechsler Adult Intelligence Scale , 1975 .

[40]  R. Lynn,et al.  Male-female differences on the Japanese WAIS-R , 1997 .

[41]  A. Karmiloff-Smith,et al.  Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. , 1999, American journal of human genetics.

[42]  A. Shiratori,et al.  Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23. , 1995, Genomics.

[43]  J. Sattler,et al.  Assessment of Children's Intelligence and Special Abilities , 1981 .

[44]  Alan S. Kaufman,et al.  Essentials of WAIS -III Assessment , 1999 .

[45]  Rumiko Matsuoka,et al.  VI. Genome Structure and Cognitive Map of Williams Syndrome , 2000, Journal of Cognitive Neuroscience.

[46]  D. Wechsler.  WAIS-R manual : Wechsler adult intelligence scale-revised , 1981 .

[47]  W. Robinson,et al.  Delineation of 7q11.2 deletions associated with Williams-Beuren syndrome and mapping of a repetitive sequence to within and to either side of the common deletion. , 1996, Genomics.

[48]  E. Zerbin-Rüdin.  [Genetics in medicine]. , 1969, Wiener medizinische Wochenschrift.

[49]  A Mari,et al.  Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes , 1999, Journal of medical genetics.

[50]  F. Ruddle,et al.  Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix-loop-helix domains. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[51]  J. Nezu,et al.  A novel family of bromodomain genes. , 2000, Genomics.

[52]  Stephan Eliez,et al.  Increased gyrification in Williams syndrome: evidence using 3D MRI methods. , 2002, Developmental medicine and child neurology.