Williams Syndrome Medline Alert - January - March 1997

January - March 1997


Record  1

7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover (letter) Urban Z; Helms C; Fekete G; Csiszar K; Bonnet D; Munnich A; Donis-Keller H; Boyd CD Am J Hum Genet (UNITED STATES) Oct 1996, 59 (4) p958-62, ISSN 0002-9297 Document type: LETTER


Record 2

Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Perez Jurado LA; Peoples R; Kaplan P; Hamel BC; Francke U Department of Genetics, Stanford University School of Medicine, CA, USA. Am J Hum Genet (UNITED STATES) Oct 1996, 59 (4) p781-92, ISSN 0002-9297 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or noninformative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at approximately 1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion.


Record 3

Williams syndrome starts making sense (editorial) Ashkenas J Am J Hum Genet (UNITED STATES) Oct 1996, 59 (4) p756-61, ISSN 0002-9297 Languages: ENGLISH Document type: EDITORIAL; REVIEW; REVIEW, TUTORIAL (37 Refs.)


Record 4

Specific eating and sleeping problems in Prader-Willi and Williams-Beuren syndrome. Sarimski K Kinderzentrum Munchen, Germany. Child Care Health Dev (ENGLAND) May 1996, 22 (3) p143-50, ISSN 0305-1862 Languages: ENGLISH Document type: JOURNAL ARTICLE
Eating and sleeping problems have a high prevalence in mental retardation in general, but are also discussed as characteristic in some genetically determined disorders. A comparative analysis of eating and sleeping behaviours in 28 Prader-Willi- and 32 Williams-Beuren syndrome children by psychometric instruments confirms excessive food-seeking behaviours in PWS and selective food refusal in WBS as specific problems. In both syndromes, however, there is considerable individual variability in these symptoms.


Record 5

A longitudinal study of cognitive abilities and educational attainment in Williams syndrome. Udwin O; Davies M; Howlin P Mary Sheridan Centre for Child Health, Lambeth Healthcare (NHS) Trust, London, UK. Dev Med Child Neurol (ENGLAND) Nov 1996, 38 (11) p1020-9, ISSN 0012-1622 Languages: ENGLISH Document type: JOURNAL ARTICLE

The paper reports on changes in IQ scores and in reading, spelling and arithmetic skills over time in 23 young adults with Williams syndrome. They were first assessed in their early to mid-teens and followed up 8 to 9 years later, at an average age of 21 years 9 months. Cognitive assessments indicated increases in Full Scale, Verbal and Performance IQ scores. These increases allow us to conclude that in the case of Williams syndrome (unlike some other conditions) there does not appear to be a decline in the rate of cognitive development over time. Comparisons of Reading, Spelling and Arithmetic scores attained at first and second testing periods revealed only modest increases in reading accuracy and spelling scores, a slight decline in reading comprehension scores, and little change in arithmetic test scores. Differences in the tests used at the two assessment periods do not allow for definitive conclusions to be drawn, but the findings suggest that individuals with Williams syndrome make little progress in their educational skills beyond their early teenage years.


Record 6

Short-term memory in children with Williams syndrome: a reduced contribution of lexical--semantic knowledge to word span. Vicari S; Carlesimo G; Brizzolara D; Pezzini G I.R.C.C.S. Ospedale Pediatrico Bambino Gesu, Santa Marinella, Rome, Italy. Neuropsychologia (ENGLAND) Sep 1996, 34 (9) p919-25, ISSN 0028-3932 Languages: ENGLISH Document type: JOURNAL ARTICLE

Williams syndrome (WS) is a genetic syndrome of abnormal neurodevelopment, characterised by a specific linguistic pattern. Comparing performances of WS subjects with those of normal children in a word span task, we found that WS subjects revealed normal phonological similarity and length effects but a reduced frequency effect. Our results suggest comparable phonological encoding mechanisms in WS and normal controls and, at the same time, it provides evidence for an impaired access to lexical-semantic knowledge in WS subjects. This dissociation fits well with the particular pattern of linguistic abilities of these subjects.


Record 7

Spontaneous regression of peripheral pulmonary artery stenosis in Williams syndrome. Miyamura H; Watanabe H; Tatebe S; Eguchi S Department of Thoracic and Cardiovascular Surgery, Niigata University School of Medicine, Japan. Jpn Circ J (JAPAN) May 1996, 60 (5) p311-4, ISSN 0047-1828 Languages: ENGLISH Document type: JOURNAL ARTICLE

An infant girl diagnosed with multiple peripheral pulmonary artery stenosis and Williams syndrome was followed-up for 17 years. Three cardiac catheterizations performed over the follow-up period showed that spontaneous gradual regression of the stenosis occurred with time. The initial systolic pressure gradient of 77-79 mmHg at the stenoses had decreased to 23-29 mmHg when measured at 17 years of age. Contrary to the progressive nature of systemic artery stenosis in Williams syndrome, peripheral pulmonary artery stenosis appears to have the capacity for spontaneous improvement. Careful consideration is required to determine the indications for interventional catheterization for the dilation of peripheral pulmonary artery stenosis in cases of Williams syndrome.


Record 8

Elastin gene deletions in Williams syndrome. Smoot LB Children's Hospital, Boston, Massachusetts, USA 02115. Curr Opin Pediatr (UNITED STATES) Dec 1995, 7 (6) p698-701, ISSN 1040-8703 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

Williams syndrome is a developmental disorder affecting predominantly connective tissue and the central nervous system. Identification of elastin mutations in families with supravalvar aortic stenosis has enabled the identification of potentially large deletions that include one elastin allele in individuals with Williams syndrome. Current efforts are aimed at defining the extent of these deletions and additional genes that contribute to the Williams syndrome phenotype. (21 Refs.)


Record 9

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. Robinson WP; Waslynka J; Bernasconi F; Wang M; Clark S; Kotzot D; Schinzel A Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. Genomics (UNITED STATES) May 15 1996, 34 (1) p17-23, ISSN 0888-7543 Languages: ENGLISH Document type: JOURNAL ARTICLE

The majority of Williams-Beuren syndrome (WBS) patients have been shown to have a microdeletion within 7q11.2 including the elastin gene locus. The extent of these deletions has, however, not been well characterized. Thirty-five deletion patients were tested for all polymorphic markers in the 7q11.2 region bounding ELN to define the extent of deletions associated with WBS. With only one exception, ELN, D7S1870, and one copy of the D7S489 locus (D7S489U) were always included in the deletions. One patient showed lack of maternal inheritance at D7S1870 and not at ELN or D7S489U. A product corresponding to D7S489U was amplified from YAC 743G6 and from the P1 clone RMC07P008, thereby localizing both to within the common deletion. The boundary of the deleted region on the proximal (centromeric) side is D7S653 and on the distal side is D7S675, neither of which were ever included in the deletion. One locus, D7S489L, was variably deleted in patients, indicating a minimum of two common breakpoints on the proximal side. At least one additional repeat amplified by D7S489 (D7S489M) was localized to a YAC contig mapping distal to the common deletion. The D7S489 sequence is highly homologous to several cDNA clones in the GenBank database and contains an Alu sequence. It is possible that this andsolidusor other repetitive sequences in this region could play a role in the mechanism of deletion.


Record 10

Sudden death in Williams syndrome: report of ten cases. Bird LM; Billman GF; Lacro RV; Spicer RL; Jariwala LK; Hoyme HE; Zamora-Salinas R; Morris C; Viskochil D; Frikke MJ; Jones MC Division of Dysmorphology, Children's Hospital, San Diego, California 92123, USA. J Pediatr (UNITED STATES) Dec 1996, 129 (6) p926-31, ISSN 0022-3476 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

Williams syndrome (WS) is a recognizable pattern of malformation with mental retardation, mild growth deficiency, characteristic facies and temperament, and cardiovascular disease. Sudden death is a recognized complication of WS; however, it is thought to be rare. The clinical features of 10 children with WS who died suddenly are reported here, doubling the number of unexpected deaths reported in the literature. We suggest that sudden death is a more common complication than has been assumed previously. Pathologic findings on the seven autopsy cases implicate two anatomic abnormalities that predispose individuals with WS to sudden death: coronary artery stenosis and severe biventricular outflow tract obstruction. The mechanisms for sudden death for both anatomic subgroups include myocardial ischemia, decreased cardiac output, and arrhythmia. We believe these observations warrant the development of strategies for monitoring patients with WS in an attempt to identify those at increased risk of sudden death. (36 Refs.)


Record 11

Williams-Beuren syndrome and celiac disease (letter) Santer R; Pankau R; Schaub J; Burgin-Wolff A J Pediatr Gastroenterol Nutr (UNITED STATES) Oct 1996, 23 (3) p339-40, ISSN 0277-2116 Languages: ENGLISH Document type: LETTER


Record 12

Molecular cytogenetic diagnosis of Williams syndrome. Hirota H; Matsuoka R; Kimura M; Imamura S; Joh-o K; Ando M; Takao A; Momma K Department of Pediatric Cardiology, Heart Institute of Japan, Tokyo Women's Medical College, Japan. Am J Med Genet (UNITED STATES) Aug 23 1996, 64 (3) p473-7, ISSN 0148-7299 Languages: ENGLISH Document type: JOURNAL ARTICLE

Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives.


Record 13

Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. Osborne LR; Martindale D; Scherer SW; Shi XM; Huizenga J; Heng HHQ; Costa T; Pober B; Lew L; Brinkman J; Rommens J; Koop B; Tsui LC Department of Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada. Genomics (UNITED STATES) Sep 1 1996, 36 (2) p328-36, ISSN 0888-7543 Languages: ENGLISH Document type: JOURNAL ARTICLE

Williams syndrome (WS) is a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Hemizygosity of the elastin (ELN) gene can account for the vascular and connective tissue abnormalities observed in WS patients, but the genes that contribute to features such as infantile hypercalcemia, dysmorphic facies, and mental retardation remain to be identified. In addition, the size of the genomic interval commonly deleted in WS patients has not been established. In this study we report the characterization of a 500-kb region that was determined to be deleted in our collection of WS patients. A detailed physical map consisting of cosmid, P1 artificial chromosomes, and yeast artificial chromosomes was constructed and used for gene isolation experiments. Using the techniques of direct cDNA selection and genomic DNA sequencing, three known genes (ELN, LIMK1, and RFC2), a novel gene (WSCR1) with homology to RNA-binding proteins, a gene with homology to restin, and four other putative transcription units were identified. LIMK1 is a protein kinase with two repeats of the LIM/double zinc finger motif, and it is highly expressed in brain. RFC2 is the 40-kDa ATP-binding subunit of replication factor C, which is known to play a role in the elongation of DNA catalyzed by DNA polymerase delta and epsilon. LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients.


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