American Journal of Medical Genetics Part AVolume 140A, Issue 10 p. 1111-1113 Research Letter A balanced reciprocal translocation in a case of hypomelanosis of Ito with confirmation of mosaicism using buccal cell interphase FISH† W.T. Keng, W.T. Keng Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorL. Harewood, L. Harewood MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorE. Grace, E. Grace Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorC. Paxton, C. Paxton Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorW.W.K. Lam, W.W.K. Lam Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorD.R. FitzPatrick, Corresponding Author D.R. FitzPatrick [email protected] Clinical Genetics Department, Western General Hospital, Edinburgh, United Kingdom MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomMRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2X, UK.Search for more papers by this author W.T. Keng, W.T. Keng Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorL. Harewood, L. Harewood MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorE. Grace, E. Grace Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorC. Paxton, C. Paxton Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorW.W.K. Lam, W.W.K. Lam Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorD.R. FitzPatrick, Corresponding Author D.R. FitzPatrick [email protected] Clinical Genetics Department, Western General Hospital, Edinburgh, United Kingdom MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomMRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2X, UK.Search for more papers by this author First published: 04 April 2006 https://doi.org/10.1002/ajmg.a.31190Citations: 3 † How to cite this article: Keng WT, Harewood L, Grace E, Paxton C, Lam WWK, FitzPatrick DR. 2006. A balanced reciprocal translocation in a case of hypomelanosis of Ito with confirmation of mosaicism using buccal cell interphase FISH. Am J Med Genet Part A 140A:1111–1113. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES Aughton DJ, AlSaadi AA, Canady AI, Lucas BM. 1993. Balanced reciprocal translocation mosaicism associated with an abnormal phenotype. Am J Med Genet 45: 721– 724. Cole TR, Hughes HE. 1994. Sotos syndrome: A study of the diagnostic criteria and natural history. J Med Genet 31: 20– 32. Duba HC, Doll A, Neyer M, Erdel M, Mann C, Hammerer I, Utermann G, Grzeschik KH. 2002. The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome. Eur J Hum Genet 10: 351– 361. Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR. 2003. Mutations in SOX2 cause anophthalmia. Nat Genet 33: 461– 463. Gardner RJ, Dockery HE, Fitzgerald PH, Parfitt RG, Romain DR, Scobie N, Shaw RL, Tumewu P, Watt AJ. 1994. Mosaicism with a normal cell line and an autosomal structural rearrangement. J Med Genet 31: 108– 114. Leegte B, Sikkema-Raddatz B, Hordijk R, Bouman K, van Essen T, Castedo S, de Jong B. 1998. Three cases of mosaicism for balanced reciprocal translocations. Am J Med Genet 79: 362– 365. Lorentz CP, Jalal SM, Thompson DM, Babovic-Vuksanovic D. 2002. Mosaic r(13) resulting in large deletion of chromosome 13q in a newborn female with multiple congenital anomalies. Am J Med Genet 111: 61– 67. Miller CA, Parker WD Jr. 1985. Hypomelanosis of Ito: Association with a chromosomal abnormality. Neurology 35: 607– 610. Ohashi H, Ishikiriyama S, Fukushima Y. 1993. New diagnostic method for Pallister-Killian syndrome: Detection of i(12p) in interphase nuclei of buccal mucosa by fluorescence in situ hybridization. Am J Med Genet 45: 123– 128. Opheim KE, Brittingham A, Chapman D, Norwood TH. 1995. Balanced reciprocal translocation mosaicism: How frequent? Am J Med Genet 57: 601– 604. Saura R, Longy M, Serville F, Chokairi O, Froute MF. 1987. Abnormal phenotype in a child with a “balanced” translocation 8/12 in mosaic state. Am J Med Genet 28: 1021– 1023. Shanske AL, Edelmann L, Kardon NB, Gosset P, Levy B. 2004. Detection of an interstitial deletion of 2q21-22 by high resolution comparative genomic hybridization in a child with multiple congenital anomalies and an apparent balanced translocation. Am J Med Genet Part A 131A: 29– 35. Stoll C, Alembik Y, Grosshans E, de Saint Martin A. 2002. An unusual human mosaic for skin pigmentation. Genet Couns 13: 281– 287. Vargas MT, Fernandez-Novoa MC. 2001. Balanced reciprocal translocation mosaicism: Clinical implications. Two new cases. Genet Couns 12: 269– 271. Citing Literature Volume140A, Issue1015 May 2006Pages 1111-1113 ReferencesRelatedInformation

Interstitial deletions of the middle portion of the long arm of chromosome 5 are relatively rare. So far, only 36 cases have been reported. Because of the repetitive banding pattern of this region, the extent and localization of the deleted segment has not been well characterized in the majority of reported cases. This has complicated attempts to establish a definite karyotype–phenotype correlation. We report a further case with a “de novo” interstitial deletion of the region 5q?15 to 5q?22 identified by standard karyotype analysis. The proband presented with failure to thrive, developmental delay, distinct craniofacial dysmorphic features, and associated structural anomalies (amongst them cleft palate, iris colobomata, and horseshoe kidney, which have previously been reported in 5q deletion cases). In addition, this child had an Arnold–Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. Use of more distal clones allowed delineation of the deleted region to 5q22.3q23.3 and to narrow down the breakpoints to approximately 200 kb. The 14 Mb deleted region contains about 60 genes but, with the possible exception of FBN2 and DMXL1, there are no obvious candidate genes for the specific components of the phenotype. This case illustrates the discrepancy between cytogenetic and molecular techniques in trying to delineate 5q interstitial deletions. Molecular studies need to be performed on these patients, to establish genotype–phenotype correlation and to understand the role and influence of genes in this region. © 2004 Wiley-Liss, Inc.

In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.

This article examines several hypotheses about the structure and level of compensation for 103 property-liability chief executive officers (CEOs) from 1995 through 1997. The greater the level of firm risk and the larger the firm, the greater the use of incentive compensation. Insurers subject to more regulatory attention and those whose CEOs have greater stock ownership make less use of incentive compensation. There is some evidence that option grants and restricted stock awards provide CEOs with differing incentives. This article finds that corporate governance structures, managers' stock ownership, and regulatory attention are not adequate to prevent CEOs from receiving compensation levels in excess of what economic factors predict. Contrary to findings in prior studies, there is little evidence that use of incentive compensation or level of total compensation paid increases with insurer investment opportunities, as traditionally measured.

We present an 11-year-old female with bullous ichthyosiform erythroderma (BIE), learning disability, patent ductus arteriosus and mild stenosis of the aortic and pulmonary arteries. Chromosome analysis showed the expression of the rare folate-sensitive fragile site FRA12A at 12q13 in 8/20 (40%) of blood lymphocytes cultured in folate-deficient medium in the presence of trimethoprim. Her mother and maternal grandmother are phenotypically normal, but her mother shows expression of the same fragile site in 4/20 (20%) of cells cultured under the same conditions. Lymphocytes from the grandmother only showed expression of the fragile site when cultured in the presence of methotrexate in folate deficient medium. Interestingly, two genes (keratin 1 and keratin 2e) which are known to cause BIE map to 12q13. Molecular data is presented excluding three candidate (CCG)n repeats within keratin 1 gene. We present a review of previously reported FRA12A cases and discuss possible molecular explanations for the clinical findings in this patient.

Summary Jacobsen syndrome iscaused bysegmental aneusomy for thedistal endofthelong armofchromosome 11.Typical features include mildtomoderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, andthrombocytopenia, though noneofthese features are invariably present. Todefine thecritical regions responsibleforthese abnormalities, westudied 17individuals with denovoterminal deletions of1q.Thepatients were characterized inaloss-of-heterozygosity

'Division of Medical Genetics, University of California, San Diego, and 'Molecular Genetics Lab, The Salk Institute, La Jolla; 3Division of Dysmorphology and Genetics, Children's Hospital, San Diego; 4Department of Genetics, Kaiser Permanente Medical Group, San Jose; 5Department of Pediatrics, Arizona Health Sciences Center, Tucson; 'Center for Human Genetics, U.Z Gasthuisberg, Leuven, Belgium; 7Department of Pathology and Cytogenetics, Royal Hospital for Sick Children, and 8Medical Genetics Service, Eastern General Hospital, Edinburgh; 9Division of Clinical Genetics and Dysmorphology, Cedars Sinai Medical Center, Los Angeles; '°Division of Genetics, University of South Florida, Tampa; "Clinica Pediatrica I Universita' di Catania, Catania, Italy; "2Murdoch Institute, Royal Children's Hospital, Melbourne; '3CSS Hospital, San Giovanni Rotondo, Italy; and '4Department of Cytogenetics, Oakwood Hospital, Dearborn, Ml

A further patient with the ICF syndrome (immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9 and 16 and facial anomalies) is described. This case is the second to be reported with consanguinity of the parents. This lends support to the theory of autosomal recessive inheritance. The features of the 15 published cases are reviewed. The clinical and cytogenetic characteristics of the syndrome are discussed, and new evidence provided as to the role of centromeres and centric heterochromatin in the production of chromosome aberrations. Correspondence with other authors has made possible a review of the clinical outcome in this condition.

In contrast to literature that has used the event study method to examine the stock market reaction to California's Proposition 103. we estimate the abnormal performance of both equally-weighted and value-weighted portfolios of securities. We also estimate a cross-sectional regression in value terms; that is. repressing the abnormal change in dollar value of the firm's equity against direct premiums written in automobile and other insurance lines in estimating relative exposure to Proposition 103. Results from the value-weighted portfolios indicate that Proposition 103 had little impact on the aggregate dollar value of the insurance industry. Cross-sectional regressions indicate that exposure, income, and size measures are not related to changes in firm value.

The Tax Reform Act (TRA) of 1986 reduced the incentives for institutional investors to participate in the tax exempt bond market. This paper develops a model of profit maximization incorporating the TRA provisions applicable to property-liability (PL) insurers. The theory predicts that PL insurers will use underwriting losses to shelter taxable investment income and invest the balance of their portfolios in tax favored securities. Our empirical evidence reveals that insurers continued to invest in tax exempts following the TRA, suggesting that implicit tax rates are low enough to attract insurers into the long-term tax exempt market. However, insurers reduced the proportions of income derived from tax exempt interest and dividends following the TRA.

Property-Liability Insurer Reserve Errors: A Theoretical and Empirical Analysis Introduction The management and reporting of income by property-liability insurers have long been legitimate concerns of regulatory and investment communities. Regulators have been concerned that investors and policyholders have fair representations of an insurer's financial status. Investors logically have been concerned with the yield and relative riskiness of their investments. When levels of risk and return are obscure to investors and regulators, stocks may not be valued properly, policyholders may not pay equilibrium-level premiums, and the ability of the firm to pay claims arising in the distant future may be difficult to judge. Detection of earnings manipulation is difficult at best, for the possibility of income management exists in every industry and differences in opinion develop over the proper measurement of income. The insurance industry is no different from other industries in its opportunities for income management. For example, the uncertainties involved in estimating future claim costs lead not only to reserve errors, but also to possible intentional income manipulation through the overstatement or understatement of reserves. Ultimately claim costs become known and the exact level of reserve errors is detected. Loomis (1984) reported that American Express received additional regulatory scrutiny in 1984 and was the defendant in an investor suit, resulting partially from reserving practices of an insurance subsidiary, Fireman's Fund, from 1978 through 1983. Reserve errors often are viewed either as a deliberate attempt by management to manipulate reported earnings, or as the result of sheer misestimation. Why management would choose to create reserve errors and whether reserve errors contribute to the value of the firm have not been developed theoretically; nor has there been much discussion of tax incentives arising from the use of reserve errors. Most of this article addresses the issue of why reserve errors arise. Specifically, the purposes of this article are to develop a theory of reserving practices of property-liability insurers and to test the theory empirically using a larger sample than do many earlier studies. It will be hypothesized that an insurer has as its objective the maximization of cash flow subject to smoothing constraints and uncertainty. Related Literature The literature on reserve estimation is exhaustive. Salzmann (1984), Peterson (1981), and Skurnik (1973), among others, have detailed numerous acceptable methods of estimating reserves. Salzmann illustrates the effects of various estimation techniques on the reserve estimates reported to regulators and investors. The studies concentrated primarily on reserving techniques, however, and made little mention of the effects of misestimation. Forbes (1969) examined auto liability reserving techniques for a sample of insurers, suggested simulation to aid in selection of optimal reserving techniques, and discussed the impact of reserving on financial statement valuations. Forbes (1970) also studied the regulation of loss reserving and found the regulation in need of reform. Anderson (1973) analyzed the effects of reserve errors on policyholders' surplus and found that reserve errors have a stabilizing effect on underwriting income. Balcarek (1975) and Ansley (1979) further related inadequate loss reserving to dismal underwriting experience in the 1970s. Ansley hypothesized that inflation was one of the major reasons for inadequate reserves in the 1970s. The investigation of reserve errors was furthered by Smith (1980), who tested whether insurers manage loss reserves to smooth underwriting results. Smith found that the incidence of overreserving and underreserving errors was not random for a sample of property-liability insurers in the auto liability line. Weiss (1985) continued the studies of Smith for a sample of insurers underwriting auto liability policies. …

A family is presented in which there were three different chromosome abnormalities in the children although the parents were cytogenetically normal. The proband had the karyotype 46,XX, r(18) (p11q23), a phenotypically normal brother was 47,XY,+mar, and another brother was a typical case of Down's syndrome, karyotype 47,XY,+21. There is nothing in the parents' history that provides grounds for a hypothesis to explain the coincidence of the abnormalities.

Tissue culture of the cells present in the urine of neonates has been demonstrated to be a suitable means of obtaining metaphase chromosomes whenever cytogenetic studies are required on cells other than blood lymphocytes. The advantages of this type of cell culture compared with the use of fibroblast culture from skin biopsy are discussed.