Epidemiology of scorpion stings in the West Bank, occupied Palestinian territory.

Background: Scorpionism (scorpion sting envenoming) is an endemic public health concern in many Arab Middle Eastern countries. However, our knowledge of the epidemiology of scorpion stings in the West Bank is limited. Aim: To investigate the epidemiology of scorpion stings in 4 districts of the West Bank over a specified period. Methods: We obtained scorpion sting records from the main hospitals in 4 districts of the West Bank for 2012 and 2014-2020. A total of 2175 cases were analyzed retrospectively using SPSS version 17. Results: The average age and standard deviation (±SD) for both sexes was 24.7±17.5 years (22.7±16.5 and 27.1±18.4 years for males and females, respectively). The median age was 20 years and 47.2% were children under 18 years. Most cases were reported during the summer months, between June and October, with a peak in July-August. By anatomic site, the right hand was the most commonly stung in both sexes, followed by the right foot. The chest, buttocks and scrotum were the least affected body parts. Clinical data were available for 405 cases, in which pain, vomiting and sweating were the most common symptoms. The overall incidence of stings was 26.32 per 100 000 inhabitants per year over the study period of 8 years (59.21-171.67, 95% CI). Conclusion: Scorpion stings are commonly encountered by adults and children in the West Bank. There is a need for awareness among the West Bank populations on how to avoid being stung, to train medical staff to better manage sting cases, and to evaluate the antivenom currently being used by physicians for scorpion stings.

Systematic list, geographic distribution and ecological significance of lady beetles (Coleoptera: Coccinellidae) from the West Bank (Central Palestine).

We surveyed and identified species of lady beetles from the West Bank to document their geographic distribution and understand their ecological significance. This study documents the presence of 35 species of Coccinellidae in 19 genera belonging to 10 tribes and 6 subfamilies. Seven species (mostly very rare), out of the 35 documented, are recorded for the first time in the area studied. These are Nephus (Bipunctatus) bipunctatus, N. crucifer, Scymnus (Scymnus) interruptus, S. (Parapullus) abietis, S. (Neopullus) limbatus, S. nigropictus, and S. (Pullus) suturalis. Nephus peyerimhoffi, introduced to Palestine in 1986 and later considered extirpated, is recorded from three localities in this study. The distribution of many species generally correlates with local biogeographical zones. All species recorded during the study feed on agricultural pests such as aphids and scale insects. Previously published accounts have been very limited, and while more remains to be done, this study is currently the most comprehensive in the West Bank.

Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: the Cancer and Leukemia Group B experience.

The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e. adequate) cases, the proportion of karyotypes whose interpretation was changed on central karyotype review. We compared the first four years during which central karyotype review was performed with a recent 4-year period and found that the proportion of rejected samples decreased significantly for both AML and ALL. However, during the latter period, central karyotype reviews still found 8% of AML and 16% of ALL karyotypes inadequate. Among adequate cases, the karyotype was revised in 26% of both AML and ALL samples. Some revisions resulted in changing the patients' assignment to particular World Health Organization diagnostic categories and/or moving patients from one prognostic group to another. Overall, when both data on rejection rates and data on karyotype revisions made in accepted cases were considered together, 32% of AML and 38% of ALL samples submitted were either rejected or revised on central karyotype review during the recent 4-year period. These data underscore the necessity of continued central karyotype review in multi-institutional cooperative group studies.

Systematics, distribution and ecological analysis of rodents in Jordan.

Distributional and ecological data were given to all rodents of Jordan. The rodent fauna of Jordan consists of 28 species with 20 genera in eight families (Cricetidae, Dipodidae, Gliridae, Hystricidae, Muridae, Myocastoridae, Sciuridae,and Spalacidae), including four introduced species.Keys for families and species were provided, along with diagnosis for each species and cranial illustrations for most species. Habitat preference and zoogeographic affinities of rodents in Jordan wereanalyzed, as well as their status and conservation.Threat categories and causes of threats on the rodents of Jordan were also analyzed.        The distribution of rodents in Jordan represents a reflection of their global distribution ranges and habitat preferences. Species associated with the temperate forest of northern Jordan includes Sciurus anomalus and two wood mice, Apodemus mystacinus and A. flavicollis, while non-forested areas are represented by Nannospalax ehrenbergi and Microtus guentheri. Strict sand dwellers include Gerbillus cheesmani and G. gerbillus. Petrophiles associated with sandstone or black lava deserts are exemplified by Acomys russatus, A. r. lewsi, H. indica and S. calurus. Others including: Jaculus jaculus, G. nanus, G. henleyi, Meriones crassus, and M. libycus are all desert-adapted species with wider ranges of distribution where scarce vegetation, wadibeds, and marabs with clay, loess, or gravel surfaces provide foraging grounds and shelter. A single species, Gerbillus dasyurus, exhibits a wide range of distribution over diverse habitat types.        The rodent fauna of Jordan consists of assemblages of different zoogeographical affinities. Nine, three, and seven were restricted or had most of its range within the Mediterranean, Irano-Turanian, and Saharo Arabian, respectively. Sciurus anomalus, Apodemus sp., Nannospalax ehrenbergi, and Microtus guentheri reached their most southern range of distribution in the Mediterranean regions of Jordan. The distribution of Gerbillus cheesmani extends from Asian deserts in India westwards into the Arabian Peninsula crossing Jordan as its most western range of distribution. Typical rodents of Saharo-Arabian affinities are represented by desert jerboas, gerbils, and jirds. North African species such as G. andersoni, G. gerbillus reached their most eastern distribution in southern Jordan. Both G. henleyi and G. nanus are widely-distributed species across North Africa reaching as far as India to the east, representing most northern outpost for these two species. Sekeetamys calurus is a nearly endemic to the Eastern Mediterranean region within southern Jordan and Sinai. Relicts are represented by Eliomys melanurus and Acomys russatus lewisi.        Several threats affecting the rodent biodiversity in Jordan were identified including habitat loss and degradation, human disturbance and related activity, legislative and public awareness. The global conservation status of the rodents of Jordan according to the IUCN Red List include 22 species as least concern, one as near threatened (Allactaga euphratica), and one as data deficient (Nannospalax ehrenbergi). According to the regional assessment, one species is critically endangered, three species are considered endangered, one vulnerable.

RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma.

CONTEXT: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. OBJECTIVE: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. DESIGN/PATIENTS: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. RESULTS: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

A novel immortalized human endometrial stromal cell line with normal progestational response.

Obtaining primary human endometrial stromal cells (HESCs) for in vitro studies is limited by the scarcity of adequate human material and the inability to passage these cells in culture for long periods. Immortalization of these cells would greatly facilitate studies; however, the process of immortalization often results in abnormal karyotypes and aberrant functional characteristics. To meet this need, we have introduced telomerase into cultured HESCs to prevent the normal shortening of telomeres observed in adult somatic cells during mitosis. We have now developed and analyzed a newly immortalized HESC line that contains no clonal chromosomal structural or numerical abnormalities. In addition, when compared with the primary unpassaged parent cells, the new cell line displayed similar biochemical endpoints after treatment with ovarian steroids. Classical decidualization response to estradiol plus medroxyprogesterone acetate were seen in both morphologically, and progestin was seen to induce or regulate the expression of IGF binding protein-1, fibronectin, prolactin, tissue factor, plasminogen activator inhibitor-1, and Fas/Fas ligand. In summary, an immortalized HESC line has been developed that is karyotypically, morphologically, and phenotypically similar to the primary parent cells, and it is a powerful and consistent resource for in vitro work.

Real-time quantitative RT-PCR of cyclin D1 mRNA in mantle cell lymphoma: comparison with FISH and immunohistochemistry.

Presence of the balanced translocation t(11;14)(q13;q32) and the consequent overexpression of cyclin D1 found in mantle cell lymphoma (MCL) has been shown to be of important diagnostic value. Although many molecular and immunohistochemical approaches have been applied to analyze cyclin D1 status, correlative studies to compare different methods for the diagnosis of MCL are lacking. In this study, we examined 39 archived paraffin specimens from patients diagnosed with a variety of lymphoproliferative diseases including nine cases meeting morphologic and immunophenotypic criteria for MCL by: (1) real-time quantitative RT-PCR to evaluate cyclin D1 mRNA expression; (2) dual fluorescence in situ hybridization (FISH) to evaluate the t(11;14) translocation in interphase nuclei; and (3) tissue array immunohistochemistry to evaluate the cyclin D1 protein level. Among the nine cases of possible MCL, seven cases showed overexpression of cyclin D1 mRNA (cyclin D1 positive MCL) and two cases showed no cyclin D1 mRNA increase (cyclin D1 negative "MCL-like"). In six of seven cyclin D1 positive cases, the t(11;14) translocation was demonstrated by FISH analysis; in one case FISH was unsuccessful. Six of the seven cyclin D1 mRNA overexpressing cases showed increased cyclin D1 protein on tissue array immunohistochemistry; one was technically suboptimal. Among the two cyclin D1 negative MCL-like cases, FISH confirmed the absence of the t(11;14) translocation in both cases. All other lymphoproliferative diseases studied were found to have low or no cyclin D1 mRNA expression and were easily distinguishable from the cyclin D1 overexpressing MCLs by all three techniques. In addition, to confirming the need to assess cyclin D1 status, as well as, morphology and immunophenotyping to establish the diagnosis of MCL, this study demonstrates good correlation and comparability between measure of cyclin D1 mRNA, the 11;14 translocation and cyclin D1 protein.

Cytogenetic abnormalities and the failure of development after round spermatid injections.

OBJECTIVE: To assess cytologic and cytogenetic abnormalities following round spermatid injection. DESIGN: Prospective analysis. SETTING: In vitro fertilization centers. PATIENT(S): Fourteen couples accepted to a round spermatid injection (ROSI) and preimplantation genetic diagnosis (PGD) program after appropriate counseling. INTERVENTION(S): ROSI, PGD, with fluorescence in situ hybridization for chromosome enumeration. MAIN OUTCOME MEASURE(S): Cytologic and cytogenetic abnormalities in oocytes, zygotes, and blastomeres. RESULT(S): The fertilization rate following ROSI was 36%. Only 11 of 143 (7.7%) oocytes developed to have several blastomeres. Cytologic and cytogenetic abnormalities accounted for the vast majority of blockage at oocyte, zygote, and early mitotic division stages. Four biopsied embryos were normal. These and seven others were implanted, but no pregnancy was achieved. CONCLUSION(S): A PGD diagnosis for common aneuploidies and blastocyst stage transfer is feasible for ROSI cases. Failure with ROSI is cause primarily by chromosome abnormalities, so use of ROSI in assisted reproductive technologies should be limited.

Telomerase prolongs the lifespan of normal human ovarian surface epithelial cells without inducing neoplastic phenotype.

OBJECTIVE: The aim of this study was to determine the effects of exogenous expression of the catalytic subunit of telomerase (hTERT) on the lifespan, growth characteristics, and tumorigenicity of normal human ovarian surface epithelial (OSE) cells. METHODS: Low-passage primary cultures of normal human OSE cells were transfected with hTERT and the resulting cell lines were characterized. RESULTS: The ectopic expression of hTERT stabilized the telomeres of the OSE cultures above 8 kb. The hTERT-transfected OSE cell lines grew beyond the normal lifespan seen in OSE cells and propagated in culture for more than 40 passages before senescing. Moreover, the hTERT-transfected cells demonstrated extensive proliferative capacity as evidenced by their ability to continuously grow even when seeded at low dilutions. The morphologic features and normal differentiation patterns seen in normal OSE cells were likewise retained by the hTERT-transfected cells. In addition, the cultures remained responsive to physiologic concentrations of epidermal growth factor and transforming growth factor-beta. Changes associated with neoplastic transformation like anchorage-independent growth, tumorigencity and karyotypic instability were not observed. CONCLUSIONS: We were able to show that the ectopic expression of hTERT in normal human OSE: 1) resulted in cultures with greater growth potential and longer lifespan and 2) did not induce a transformed phenotype previously seen in viral oncogene-transfected OSE cells. The established cell lines would not only provide sufficient material for comprehensive studies to investigate the normal physiology of OSE cells, but could also help in the understanding of the early steps of ovarian carcinogenesis.

Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis.

BACKGROUND: The World Health Organization recently recognized a family of neoplasms showing at least partial morphological or immunohistochemical evidence of a putative perivascular epithelioid cell (PEC) differentiation. These tumors include angiomyolipoma (AML), clear cell "sugar" tumors of the lung (CCST), lymphangioleiomyomatosis (LAM), clear cell myomelanocytic tumors of the falciform ligament and distinctive clear cell tumors at various other anatomic sites. CASE PRESENTATION & METHODS: A 41-year old gravida-1 para-1 with tuberous sclerosis presented with an incidentally identified 2.2 cm mass. The morphology and immunohistochemical profile was consistent with PEComa. Distinct aggregates of HMB-45 epithelioid cells were present in an occasionally distinctive perivascular distribution in the myometrium, small bowel lamina propria and ovarian hila. These distinctive aggregates, for which we propose the designation "PEComatosis" based on their intraabdominal distribution, did not display cytological atypia, mitotic activity or necrosis. CGH and DNA ploidy analysis showed a balanced chromosomal profile and diploid nuclei, respectively. There was no recurrence or metastases at 35 months' follow-up. Fifty-one previously reported cases of non-AML, LAM and CCST PEComas [perivascular epithelioid cell tumors- not otherwise specified (PEComa-NOS)] are reviewed. CONCLUSIONS: The lesions may be a reflection of tumor multicentricity, in which each may be a potential nidus for the development of future more well-developed tumors. Alternatively, they may be a manifestation of a poorly understood "field effect", in which there is an increased propensity to develop tumors of this type throughout the abdomen. Finally, and least likely in our opinion, they may represent tumor spread from its primary site.

Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization.

BACKGROUND: Routine cytogenetic investigations for ovarian cancers are limited by culture failure and poor growth of cancer cells compared to normal cells. Fluorescence in situ Hybridization (FISH) application or classical comparative genome hybridization techniques are also have their own limitations in detecting genome imbalance especially for small changes that are not known ahead of time and for which FISH probes could not be thus designed. METHODS: We applied microarray comparative genomic hybridization (A-CGH) using one mega base BAC arrays to investigate chromosomal disorders in ovarian adenocarcinoma in patients with familial history. RESULTS: Our data on 10 cases of ovarian cancer revealed losses of 6q (4 cases mainly mosaic loss), 9p (4 cases), 10q (3 cases), 21q (3 cases), 22q (4 cases) with association to a monosomy X and gains of 8q and 9q (occurring together in 8 cases) and gain of 12p. There were other abnormalities such as loss of 17p that were noted in two profiles of the studied cases. Total or mosaic segmental gain of 2p, 3q, 4q, 7q and 13q were also observed. Seven of 10 patients were investigated by FISH to control array CGH results. The FISH data showed a concordance between the 2 methods. CONCLUSION: The data suggest that A-CGH detects unique and common abnormalities with certain exceptions such as tetraploidy and balanced translocation, which may lead to understanding progression of genetic changes as well as aid in early diagnosis and have an impact on therapy and prognosis.

CytoAccess, a relational laboratory information management system for a clinical cytogenetics laboratory.

We developed a CytoAccess laboratory management system based on the widely used Microsoft Access software to facilitate data processing, result reporting, and quality management for a full-service cytogenetics laboratory. The CytoAccess system consists of four functional modules. The data entry module is for logging in patient information. The result entry module is used to generate chromosome, fluorescent in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) reports. The administrative module enables periodic monitoring of quality control and quality improvement (QA/QI) parameters and produces billing forms. The maintenance module allows users to update clinical demographics, report templates, code tables, and to refresh data links. We have integrated into this system over 15,000 chromosome and FISH results from prenatal, postnatal, and cancer cases for the past six years. This system is cost-effective, user-friendly, flexible in updating, and potentially adaptable for data mining.

Karyotype-phenotype insights from 11q14.1-q23.2 interstitial deletions: FZD4 haploinsufficiency and exudative vitreoretinopathy in a patient with a complex chromosome rearrangement.

We detected a unique de novo complex chromosome rearrangement (CCR) in a patient with multiple abnormalities including growth retardation, facial anomalies, exudative vitreoretinopathy (EVR), cleft palate, and minor digital anomalies. Cytogenetic analysis, fluorescent in situ hybridization, and microsatellite genotyping showed a reciprocal translocation between chromosomes 5 and 8, and a complex translocation-deletion-inversion process in the formation of derivative chromosomes 11 and 16. High-density whole-genome oligonucleotide array comparative genomic hybridization (oaCGH) defined a 35-megabase interstitial deletion of 11q14.1-q23.2 and a 1 megabase deletion of 16q22.3-q23.1. The Frizzled-4 (FZD4) gene is located within this 11q deletion. Parental studies and sequencing analysis confirmed that the patient was hemizygous for FZD4 due to the loss of a paternal allele on the derivative chromosome 11. Mutations in FZD4 are known to cause autosomal dominant exudative vitreoretinopathy (EVR1). Our patient's findings suggest that haploinsufficiency of the FZD4 gene product can also be a disease-causing mechanism for EVR1. We reviewed the clinical manifestations of 23 cases with 11q14-q23 interstitial deletions, with particular scrutiny of the present case and four reported cases characterized by molecular cytogenetics. These findings were used to construct a regional deletion map consisting of a haplosufficient segment at 11q14.3, a flanking centromeric segment at 11q14.1-q14.2, and a flanking telomeric segment at 11q21-q23.3. We propose that deletions of the FZD4 gene located within the centromeric segment cause retinal dysgenesis, while deletions within the telomeric segment account for dysmorphic craniofacial features, growth and mental retardation, and mild digital anomalies. These results provide insight into karyotype-phenotype correlations and prompt a rational analytic approach to cases with interstitial deletions of the 11q14-q23 region.

Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461.

We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex > or = 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex > or = 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex > or = 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex > or = 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P < .001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex > or = 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.

Natural killer cell lymphoma/leukemia with homozygous loss of p27/kip1.

We describe a case of natural killer (NK) cell lymphoma/leukemia with only an interstitial deletion in the short arm of chromosome 12 as the primary event. Fluorescence in situ hybridization revealed that the ETV6 locus (12p13) and subtelomeric sequences are not deleted in the process. The p27/kip1 locus (12p12-13), a candidate tumor suppressor gene, was deleted on the abnormal chromosome. Sequence analysis detected an adenine nucleotide deletion in the third codon of exon 1 leading to frameshift and premature termination at codon 41 of the retained copy of p27/kip1. To the best of our knowledge, this is the first report in literature on a NK cell lymphoma/leukemia with complete loss of p27/kip1.

Rapid array-based genomic characterization of a subtle structural abnormality: a patient with psychosis and der(18)t(5;18)(p14.1;p11.23).

Array-based copy number analysis has recently emerged as a rapid means of mapping complex and/or subtle chromosomal abnormalities. We have compared two such techniques, using bacterial artificial chromosome (BAC) and single nucleotide polymorphism (SNP) arrays in the evaluation of a 45-year-old woman with dysmorphic features, mental retardation, psychosis, and an unbalanced derivative chromosome 18, (46,XX, der(18)t(18;?)(p12;?)). Both array-based methods demonstrated that the additional material on chromosome 18 was of 5p origin. The 5p duplication mapped telomeric to 25.320 Mb (BAC array) and 25.607 Mb (SNP array), corresponding to the band 5p14.1. Both BAC and SNP arrays also showed a deletion involving chromosome 18p extending telomeric from 8.437 Mb (BAC array) and 8.352 Mb (SNP array), corresponding to the band 18p11.23. Molecular cytogenetic mapping using fluorescence in situ hybridization (FISH) supported the array findings and further refined the breakpoint regions, confirming that the BAC and SNP chips were both useful in this regard. Both case reports and linkage analyses have implicated these chromosomal intervals in psychosis. The array-based experiments were completed over the course of several days. While these methods do not eliminate the requirement for traditional fine-mapping, they provide an efficient approach to identifying the origin and extent of deleted and duplicated material in chromosomal rearrangements.

FOXC1 gene deletion is associated with eye anomalies in ring chromosome 6.

We report a case of ring chromosome 6 presenting with growth and mental retardation, cerebral dysgenesis, eye malformations, mixed hearing loss, and abnormal physical features. Fluorescent in situ hybridization (FISH) and microsatellite genotyping demonstrated segmental deletions of less than 6 Mb on 6p and 1-2 Mb on 6q. The primary karyotype is designated as 46,XY,r(6)(p25q27).ish r(6)(p25.1q27)(D6S344-, FOXC1-, D6S1574+, D6S281-, D6S297+). Secondary structural and numerical variants of the ring 6 were observed in 16% of the cells analyzed. Intragenic genotyping revealed deletion of the paternal FOXC1 gene, haploinsufficiency of which has been reported to cause eye anterior chamber developmental defects. Accordingly, we propose that our patient's ophthalmologic abnormalities result from haploinsufficiency of the transcription factor FOXC1. We present clinical and cytogenetic summaries on 23 reported cases of ring 6 and categorize them into mild, moderate, and severely affected groups. Further phenotype comparisons between cases with ring 6 and cases with only 6p or 6q terminal deletions suggest that genes important for hearing, vision, and central nervous system development remain to be identified in chromosome 6 terminal regions. Molecular definition of the fusion points and tissue mosaicism studies are necessary to better understand the genotype-phenotype correlation of ring 6. We recommend ophthalmology, audiology, cardiology, and central nervous system examinations be part of the routine evaluation for children with a ring chromosome 6.

Double supernumerary isodicentric chromosomes derived from 15 resulting in partial hexasomy.

We report two unrelated patients each with two supernumerary marker chromosomes (SMCs) derived from chromosome 15, and thus resulting in partial hexasomy. Hexasomy in the one case (family 1) was diagnosed at prenatal diagnosis and did not include the Prader-Willi/Angelman critical region (PWACR). The double SMCs were also found in the mother, the pregnancy continued to term, and an apparently phenotypically normal child was born. This represents the first report of transmission of double SMCs from mother to child. In the second case (family 2), the hexasomy did include the PWACR and was de novo in origin. This patient manifested severe psychomotor retardation, clefting of the soft palate, hypotonia, seizure-like episodes, and other phenotypic features. The aberrant phenotype is attributable to the hexasomy for the PWACR gene loci. The normal homologs of chromosome 15 proved to be biparental in origin while the two SMCs appeared maternal.