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Introduction: Distinguishing paracentric inversions (PAIs) from chromosomal insertions has traditionally relied on fluorescent in situ hybridization (FISH) techniques, but recent advancements in high‐throughput sequencing have enabled the use of genome sequencing for such differentiation. In this study, we present a 38‐year‐old male carrier of a paracentric inversion on chromosome 2q, inv (2)(q31.2q34), whose partner experienced recurrent miscarriages. Material and Methods: FISH analysis confirmed the inversion, and genome sequencing was employed for detailed characterization. Results: Preimplantation genetic testing (PGT) revealed that all assessed embryos were balanced, consistent with the low risk of unbalanced offspring associated with PAIs. While PAI carriers traditionally exhibit low risk of producing unbalanced offspring, exceptions exist due to crossover events within the inversion loop. Although the sample size was limited, the findings align with existing sperm study data, supporting the rare occurrence of unbalanced progeny in PAI carriers. Conclusions: This study highlights the possibility of characterizing PAIs using genome sequencing to enable correct reproductive counseling and PGT decisions. Detailed characterization of a PAI is crucial for understanding potential outcomes and guiding PGT strategies, as accurate knowledge of the inversion size is essential for appropriate method selection in PGT. Given the very low risk of unbalanced offspring in PAI carriers, routine PGT may not be warranted but should be considered in specific cases with a history of unbalanced progeny or recurrent miscarriages. This study contributes to our understanding of PAI segregation and its implications for reproductive outcomes. [ABSTRACT FROM AUTHOR]

Objectives Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare group of neoplasms that share features of eosinophilia and lineage promiscuity. First, we described a challenging case of acute leukemia with lineage switch and cytogenetically cryptic FGFR1. Second, we aimed to systemically review this phenomenon in published literature. Methods A 68-year-old man with a history of chemotherapy exposure presented with acute leukemia of myeloid lineage without eosinophilia or 8p11 abnormalities on karyotyping. Over a refractory and relapsing course, the blast phenotype shifted to B lymphoid. Results Fluorescence in situ hybridization identified a cytogenetically cryptic FGFR1 rearrangement, likely a paracentric inversion. We identified 26 published cases of FGFR1 -rearranged acute leukemia with ambiguous, mixed, or switching lineage. Although there was variability in the partner gene, anatomical location of different phenotypes, and timing of lineage switch, the prognosis was consistently poor in the absence of novel therapy. Conclusions Ours is the only reported case of FGFR1 -rearranged neoplasms with a disease sequence of acute myeloid leukemia transforming to B-cell acute lymphoblastic leukemia and 1 of only 3 reported cases with cytogenetically cryptic FGFR1 rearrangement. Fluorescence in situ hybridization testing for FGFR1 rearrangement should be a standard investigation in leukemia of mixed or switching lineage. [ABSTRACT FROM AUTHOR]

Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling. [ABSTRACT FROM AUTHOR]

Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling.

The genus Mazama stands out among the Neotropical deer due to their wide intra and interspecific karyotypic diversification, which is associated with an accentuated chromosomal fragility. There are reports of heterozygous Robertsonian translocation (RT) carriers in a free-range population of Mazama gouazoubira (brown brocket deer), as well as in captive animals of this and other species of the genus. To analyze possible negative impacts of heterozygous chromosome rearrangements on reproductive fitness of the carriers, we performed an analysis of sperm meiotic segregation in four brown brocket bucks, carriers of a rob(4;16), and compared the results with those of a normal buck. We established a reliable FISH and sperm-FISH protocol for the brown brocket deer using bovine (Bos taurus ; diploid number, 2n = 60) whole chromosome painting (WCP) and BAC probes. Using BAC probes, we revealed the presence of a paracentric inversion (PAI) of the fused chromosome 4 in two of the four analyzed RT carriers. The mean frequency of normal/balanced sperm in the translocation carriers was significantly lower than in the normal buck (94.78% vs 98.40%). The mean value of total unbalanced spermatozoa was almost doubled in the RT/PAI carriers (6.68%) when compared to RT carriers (3.76%), but the difference was not statistically significant. This study demonstrated the efficiency of FISH with bovine WCP and BAC probes in the characterization of chromosome rearrangements and gametic segregation patterns in brown brocket deer. Our results indicate a low to moderate increase in the rates of unbalanced meiotic segregation products in brown brocket bucks heterozygous for RT and RT/PAIs. • Presence of heterozygous rob(4;16) and rob(4;16)inv(4) in M. gouazoubira. • First report of FISH on M. gouazoubira sperm nuclei using bovine BAC probes. • Low to moderate rates of unbalanced meiotic segregation products of the carriers. [ABSTRACT FROM AUTHOR]

Usher type 1 syndrome is a rare autosomal recessive disorder involving congenital severe-to-profound hearing loss, development of vision impairment in the first decade, and severe balance difficulties. The PCDH15 gene, one of the five genes implicated in this disease, is involved in 8–20% of cases. In this study, we aimed to identify and characterize the two causal variants in a French patient with typical Usher syndrome clinical features. Massively parallel sequencing-based gene panel and screening for large rearrangements were used, which detected a single multi-exon deletion in the PCDH15 gene. As the second pathogenic event was likely localized in the unscreened regions of the gene, PCDH15 transcripts from cultured nasal cells were analyzed and revealed a loss of junction between exon 13 and exon 14. This aberration could be explained by the identification of two fusion transcripts, PCDH15-LINC00844 and BICC1-PCDH15, originating from a 4.6 Mb inversion. This complex chromosomal rearrangement could not be detected by our diagnostic approach but was instead characterized by long-read sequencing, which offers the possibility of detecting balanced structural variants (SVs). This finding extends our knowledge of the mutational spectrum of the PCDH15 gene with the first ever identification of a large causal paracentric inversion of chromosome 10 and illustrates the utility of screening balanced SVs in an exhaustive molecular diagnostic approach.

Usher type 1 syndrome is a rare autosomal recessive disorder involving congenital severe-to-profound hearing loss, development of vision impairment in the first decade, and severe balance difficulties. The PCDH15 gene, one of the five genes implicated in this disease, is involved in 8–20% of cases. In this study, we aimed to identify and characterize the two causal variants in a French patient with typical Usher syndrome clinical features. Massively parallel sequencing-based gene panel and screening for large rearrangements were used, which detected a single multi-exon deletion in the PCDH15 gene. As the second pathogenic event was likely localized in the unscreened regions of the gene, PCDH15 transcripts from cultured nasal cells were analyzed and revealed a loss of junction between exon 13 and exon 14. This aberration could be explained by the identification of two fusion transcripts, PCDH15 - LINC00844 and BICC1 - PCDH15 , originating from a 4.6 Mb inversion. This complex chromosomal rearrangement could not be detected by our diagnostic approach but was instead characterized by long-read sequencing, which offers the possibility of detecting balanced structural variants (SVs). This finding extends our knowledge of the mutational spectrum of the PCDH15 gene with the first ever identification of a large causal paracentric inversion of chromosome 10 and illustrates the utility of screening balanced SVs in an exhaustive molecular diagnostic approach. [ABSTRACT FROM AUTHOR]

Aims: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia‐associated transcription factor family on chromosome Xp11.2. Dual‐colour break‐apart fluorescence in‐situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA‐binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10–TFE3 fusion results from paracentric inversion. RBM10–TFE3 RCC may yield a false‐negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10–TFE3 RCC. Methods and results: Ten patients with RBM10–TFE3 RCC aged 31–71 years were investigated. Histological analysis, immunostaining, dual‐colour break‐apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. Conclusions: The present study suggests that the carcinogenesis of RBM10–TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10–TFE3 RCC should be considered, as five patients experienced metastases. [ABSTRACT FROM AUTHOR]

Partial trisomies have often been reported secondary to inversion mutations. These occurrences are most frequently associated with pericentric inversions. In this report, we describe the first documented case of partial trisomy 13 secondary to a parental paracentric inversion, in this case a paternal paracentric 13q inversion. Our Patient exhibits a variety of clinical findings including global developmental delay with intellectual disability, sensorineural hearing loss, bilateral congenital polar cataracts with associated foveal and optic nerve hypoplasia, right retinal detachment, atrial septal defect, absence of corpus callosum, celiac disease, microcephaly, as well as other dysmorphic features. [ABSTRACT FROM AUTHOR]

Introduction. Autism spectrum disorders (ASDs) are a group of complex pervasive developmental disorders characterized by impairments in communication, social interaction and behavior. In most cases autism is caused by a combination of genetic factors and environmental risk factors. In 10% to 20% of cases it has been shown that the cause of ASD is genetic. Case Outline. We are describing a 2-year-old boy who was referred to genetic counseling because of speech delay and certain autism-like behavior. By cytogenetic analysis the karyotype 46, inv(X),Y was obtained. The boy was a carrier of a paracentric inversion of the short arm of the chromosome X. After cytogenetic analysis of parental blood, it was detected that mother was a carrier of identical aberration, but had no clinical signs. The method of fluorescent in situ hybridization (FISH) yielded the precise breakpoint in the region (p21.2p11.23). Mother and son were carriers of identical X chromosome. Conclusion. Breakpoints are located in the regions that have already been linked to autism, which indicates that the positional effect of the gene could have been a possible cause of the patient’s genotype. In addition to positional effects, in order to better understand the etiology of autism other genetic and environmental factors should be always taken into consideration. [Projekat Ministarstva nauke Republike Srbije, br. ON175013]

Pimelodidae is one of the most representative of Neotropical catfish families. However, these fish are still poorly studied in terms of cytogenetics, especially regarding the application of more accurate techniques such as the chromosomal localization of ribosomal genes. In the present work, fluorescent in situ hybridization with 5S and 18S rDNA probes was employed for rDNA site mapping in Pimelodus sp., P. fur and P. maculatus from the São Francisco River in the Três Marias municipality - MG. The results from the application of the 18S probe confirmed the previous data obtained by silver nitrate staining, identifying a simple nucleolar organizing region system for these species. However, the labeling results from the 5S rDNA probe demonstrated a difference in the number and localization of these sites between the analyzed species. The obtained data allowed inferences on the possible processes involved in the karyotypic evolution of this genus.

Cytogenetic analysis with Astyanax sp. D revealed a karyotype of 2n=50 with 2M+26SM+6ST+16A, besides a triploid specimen showing 2n=75 chromosomes (3M+39SM+9ST+24A). C-banding strongly stained the terminal regions of several SM-ST-A chromossomes. Two pairs of acrocentric chromosomes presented interstitial heterochromatin, this state being polymorphic and occuring due to possible paracentric inversions. The results obtained with the AluI restriction enzyme and A3 chromomycin were similar to the C-banding. Relationships were proposed between Astyanax sp. D and A. scabripinnis, as well as considerations for a possible origin of the triploid specimen (2n=3x=75). When comparing the present results with cytogenetic features of other endemic Astyanax species in the Iguaçu river (A. sp. B and C), a clear differentiation was observed between them, indicating cytogenetics as an important cytotaxonomic tool.Análises citogenéticas em Astyanax sp. D evidenciaram 2n=50 cromossomos e um cariótipo com 2M+26SM+6ST+16A. O bandamento C destacou as regiões teloméricas de diversos cromossomos SM-ST-A. Dois pares de cromossomos acrocêntricos possuem heterocromatina intersticial, sendo este estado polimórfico decorrente de prováveis inversões paracêntricas. O resultados obtidos com a enzima de restrição AluI e a Cromomicina A3 foram semelhantes aos do bandamento C. São propostas relações de parentesco entre Astyanax sp. D e Astyanax scabripinnis, bem como considerações sobre a possível origem do exemplar triplóide (2n=3x=75). Ao comparar os resultados deste trabalho com outras espécies de Astyanax do Rio Iguaçu, estas espécies se tornam claramente distinguíveis, evidenciando a citogenética como uma importante ferramenta taxonômica.

Cytogenetic analysis of a rainbow trout stock showed that the nucleolar organizing regions were located subterminally on the long arm of a submetacentric chromosome pair and occurred as a single chromosomal segment (phenotype N1) or as two chromosomal segments separated by a short euchromatic segment (phenotype N2). Cytogenetic analysis also showed that there were N1N1 and N1N2 individuals but no N2N2 individuals. Analysis of the different includedphenotypes incluted that the population was not in Hardy-Weinberg equilibrium (chi² = 19.333; p < 0.01), and that a higher frequency of individuals had the N1N2 phenotype. Experimental crosses involving four males (two N1N1 and two N1N2) and four females (one N1N1 and three N1N2) yielded eight broods. There were no significant differences between the expected and observed frequencies of offspring resulting from crosses involving N1N1 x N1N2 individuals. However, significant differences were seen in crosses involving N1N2 x N1N2 parents because of the a high incidence of N1N2 fishes and the absense of N2N2. The lack of N2N2 individuals in the parental sample and their absence among the offspring of the experimental crosses suggested that this genetic combination may be lethal in rainbow trout. The survival rates of embryonic "eyed egg" and fry stage individuals were not different, indicating that the possible lethal effect may occur during more advanced ontogenetic phases.

Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Structural chromosome changes are widely described in different vertebrate groups and generate genetic, phenotypic and behavioral diversity. During the evolution of loricariids, several rearrangements (fissions, fusions, inversions) seem to have occurred. Hypancistrus, tribe Ancistrini, are highly demanded for fishkeeping around the world. In this tribe, the diploid chromosome number 2n = 52 is considered a synapomorphy, and paracentric-type inversions appear to be involved in the chromosomal evolution of the tribe. The present study investigated the karyotypes of H. zebra and H. cf. debilittera using cytogenetic, classical and molecular tools, as well as DNA barcoding. Data reveal that, although diploid number in both species corroborates the proposed synapomorphy for the tribe, there is a complex karyotype dynamics, reflected in the intense chromosomal polymorphism, resulting from rearrangements involving ribosomal regions (5S and 18S rDNA), which are suggested to be paracentric inversions. Besides, DNA barcode confirms reciprocal monophyletism between the species, validating the existence of two species, only. This scenario, coupled with genomic instability caused by exogenous sequences such as Rex-3 retrotransposons and the species' sedentary lifestyle, which helps the fast polymorphism fixation, may reflect different phenotypic color patterns in natural populations, as observed in H. cf. debilittera. [ABSTRACT FROM AUTHOR]

We report on a 26-month-old boy with an interstitial duplication of 2p22.3p22.2 and an interstitial deletion of 2q14.1q21.2. The abnormality was derived from his father having a balanced paracentric inversion and pericentric insertion. The deletion in the child was identified by cytogenetic analysis and characterized in more detail by molecular cytogenetics and array comparative genomic hybridization. The latter revealed a 20-Mb deletion in the long arm and a 5.6-Mb duplication in the short arm of chromosome 2. Fluorescence in situ hybridization in paternal chromosomes characterized an intrachromosomal insertion of 2q14.1q21.2 into 2p23; additionally a paracentric inversion of 2p13p23 was observed. The boy with the unbalanced karyotype suffered from severe psychomotor retardation, thrombophilia due to protein C deficiency, and hypertrophic cardiomyopathy and also had phenotypic abnormalities. Most of these features have previously been described in individuals with interstitial deletion of 2q14.1. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Meningiomas are classified as benign, atypical, or anaplastic. The majority are sporadic, solitary, and benign tumors with favorable prognoses. However, the prognosis for patients with anaplastic meningiomas remains less favorable. High resolution genomic profiling has the capacity to provide more detailed information. Therefore, we analyzed genomic aberrations of benign and atypical meningiomas using single nucleotide polymorphism (SNP) array, combined with G-banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently detected chromosomal aberrations in meningiomas and identified novel genetic events. Applying SNP array, we identified constitutional de novo loss or gain within chromosome 22 in three patients, possibly representing inherited causal events for meningioma formation. We show evidence for somatic segmental uniparental disomy in regions 4p16.1, 7q31.2, 8p23.2, and 9p22.1 not previously described for primary meningioma. GTG-banding and spectral karyotyping detected a novel balanced reciprocal translocation t(4;10)(q12;q26) in one benign meningioma. A paracentric inversion within 1p36, previously described as novel, was detected as a recurrent chromosomal aberration in benign and atypical meningiomas. Analyses of tumors and matched normal tissues with a combination of SNP arrays and complementary techniques will help to further elucidate potentially causal genetic events for tumorigenesis of meningioma. [Copyright &y& Elsevier]

Abstract: Carriers of paracentric inversions (PAIs) are usually asymptomatic. However, such inversions may lead to the formation of recombinant gametes and then to an abnormal gestation. Here we report a girl with a 7q31.32 → q33 deletion secondary to a maternal PAI of chromosome 7. This finding was confirmed through FISH and whole-genome array-CGH analyses. The deficiency of the chromosome 7 observed in our patient was never described before and we did not find any known gene localized within the deficient segment that could be related to her findings of hypoplastic iliac bones, hypoplastic labia minora and postaxial polydactyly. This case highlights the fact that rare viable recombinants can be developed from PAIs, an issue that must be discussed in the genetic counseling. [Copyright &y& Elsevier]

Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint (∼108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation. [ABSTRACT FROM AUTHOR]

Paracentric inversions (PAIs) are structural chromosomal rearrangements generally considered to be harmless. To date, only a few studies have been performed concerning the meiotic segregation of these rearrangements, using either the human–hamster fertilization system or fluorescence in situ hybridization (FISH) with centromeric or telomeric DNA probes. To improve the assessment of imbalances in PAI, we present a new strategy based on FISH assay using multiple bacterial artificial chromosome probes, which allow a precise localization of chromosome break points and the identification of all meiotic products in human sperm. Sperm samples of three cases with PAI were investigated: an inv(5)(q13.2q33.1), an inv(9)(q21.2q34.13) and an inv(14)(q23.2q32.13). The frequencies of spermatozoa with inverted chromosomes were 44.7% in inv(5), 42.7% in inv(9) and 46.7% in inv(14). The global incidences of unbalanced complements were 9.7, 12.6 and 3.7% in inv(5), inv(9) and inv(14), respectively. This report is the first study providing a detailed description of meiotic segregation patterns in human sperm by using a sperm FISH approach. This study demonstrates that the detailed analysis of segregation in PAI may provide important data for both genetic analysis and counseling of inversion carriers.European Journal of Human Genetics (2009) 17, 44–50; doi:10.1038/ejhg.2008.144; published online 6 August 2008 [ABSTRACT FROM AUTHOR]

Autism is a genetic neurodevelopmental disorder of unknown cause and pathogenesis. The identification of genes involved in autism is expected to increase our understanding of its pathogenesis. Infrequently, neurodevelopmental disorders like autism are associated with chromosomal anomalies. To identify candidate genes for autism, we initiated a positional cloning strategy starting from individuals with idiopathic autism carrying a de novo chromosomal anomaly. We report on the clinical, cytogenetic and molecular findings in a male person with autism, no physical abnormalities and normal IQ, carrying a de novo balanced paracentric inversion 46,XY,inv(10)(q11.1;q21.3). The distal breakpoint disrupts the TRIP8 gene, which codes for a protein predicted to be a transcriptional regulator associated with nuclear thyroid hormone receptors. However, no link between thyroid gland and autism has been reported so far. In addition, the same breakpoint abolishes expression of a nearby gene, REEP3, through a position effect. Receptor Expression-Enhancing Proteins (REEP) 3 is one of the six human homologs of yeast Yop1p, a probable regulator of cellular vesicle trafficking between the endoplasmatic reticulum and the Golgi network. These observations suggest that TRIP8 and REEP3 are both positional candidate genes for autism. In addition, our data indicate that in the selection of positional candidate genes when studying chromosomal aberrations, position effects should be taken into account.European Journal of Human Genetics (2007) 15, 422–431. doi:10.1038/sj.ejhg.5201785; published online 7 February 2007 [ABSTRACT FROM AUTHOR]

Abstract: The existence of transcripts that span two adjacent, independent genes is considered rare in the human genome. This study characterizes a novel human fusion gene named IQCJ–SCHIP1. IQCJ–SCHIP1 is the longest isoform of a complex transcriptional unit that bridges two separate genes that encode distinct proteins, IQCJ, a novel IQ motif containing protein and SCHIP1, a schwannomin interacting protein that has been previously shown to interact with the Neurofibromatosis type 2 (NF2) protein. IQCJ–SCHIP1 is located on the chromosome 3q25 and comprises a 1692-bp transcript encompassing 11 exons spanning 828kb of the genomic DNA. We show that IQCJ–SCHIP1 mRNA is highly expressed in the brain. Protein encoded by the IQCJ–SCHIP1 gene was localized to cytoplasm and actin-rich regions and in differentiated PC12 cells was also seen in neurite extensions. [Copyright &y& Elsevier]

Abstract: Specific language impairment (SLI) is defined as failure to acquire normal language skills despite adequate intelligence and environmental stimulation. Although SLI disorders are often heritable, the genetic basis is likely to involve a number of risk factors. This study describes a 7-year-old girl carrying an inherited paracentric inversion of the long arm of chromosome 3 [46XX, inv(3)(q25.32–q29)] having clinically defined expressive and receptive language delay. Fluorescence in situ hybridization (FISH) with locus-specific bacterial artificial chromosome clones (BACs) as probes was used to characterize the inverted chromosome 3. The proximal and distal inversion breakpoint was found to reside between markers D3S3692/D3S1553 and D3S3590/D3S2305, respectively. ATP13A4, a novel gene coding for a cation-transporting P-type ATPase, was found to be disrupted by the distal breakpoint. The ATP13A4 gene was shown to comprise a 3591-bp transcript encompassing 30 exons spanning 152 kb of the genomic DNA. This study discusses the characterization of ATP13A4 and its possible involvement in speech-language disorder. [Copyright &y& Elsevier]

Chromosome specific painting probes of human, sheep and the Hirola antelope ( Damaliscus hunteri) derived by flow sorting of chromosomes were used in multi directional chromosome painting experiments to better define the karyological relationship within Bovidae species (specifically, Caprini and Alcelaphini tribes) and humans. Although not all chromosomes of Damaliscus hunteri could be resolved into single peaks by flow-sorting we managed to present a complete homology map for chromosomes between the three species. When comparing the karyotype of Damaliscus hunteri with human all of the main known motives in mammalian chromosome evolution are present (i.e. associations of human homologous chromosomes 3–21, 4–8, 7–16, 14–15, 16–19 and two forms of 12–22) which were also confirmed with the sheep paint probes. Further, we observed those patterns that have been described as common derived traits for artiodactyls (i.e. associations of human homologous chromosomes 5/19 and a complex alternating pattern of hybridizations with human chromosome 14 and 15 probes). As known from classical karyotyping some of the Damaliscus chromosomes are biarmed and were supposedly involved in Robertsonian translocations frequently found in karyotype evolution of bovids. We refined these rearrangements with the molecular probes and also delineated a chromosome painting pattern that should be the result of a paracentric inversion in the Damaliscus hunteri karyotype. This study demonstrates that multidirectional chromosome painting will be a valuable tool for the investigation of the dynamics of chromosome evolution in exotic bovid species. [ABSTRACT FROM AUTHOR]

A new case of familial heterozygous paracentric inversion in the long arm of chromosome 14 [inv(14)(q22q32)] is presented. The rearrangement was first ascertained in a fetus examined due to advanced maternal age, and then detected in the father. The phenotypes of the newborn and the father were completely normal. The parents had no history of spontaneous abortion. With reference to previous reports, the risk of clinical abnormalities are discussed for both de novo and familial paracentric inversions of chromosome 14. [ABSTRACT FROM AUTHOR]

An eight-year-old girl with bilateral facial paresis and restricted eye movements was diagnosed with Moebius syndrome. A chromosomal analysis showed a paracentric inversion on the long arm of chromosome 8 (46, XX, inv(8) (q21.3q24.13)). Candidate genes have been found on chromosomes 3q21, 10q21, and 13q12. We discuss the genes which are known to have associated ocular movement dysfunction in the 8q21-24 region. We hope this case will add to the current body of knowledge regarding Moebius syndrome and its genetics. [ABSTRACT FROM AUTHOR]