RESUMO
Nephropathic cystinosis, an autosomal recessive disorder resulting from defective lysosomal transport of cystine, is the most common inherited cause of renal Fanconi syndrome. The cystinosis gene has been mapped to chromosome 17p13. We found that the locus D17S829 was homozygously deleted in 23 out of 70 patients, and identified a novel gene, CTNS, which mapped to the deletion interval. CTNS encodes an integral membrane protein, cystinosin, with features of a lysosomal membrane protein. Eleven different mutations, all predicted to cause loss of function of the protein, were found to segregate with the disorder.
Assuntos
Cistinose/genética , Genes/genética , Glicoproteínas , Nefropatias/genética , Proteínas de Membrana/genética , Sequência de Aminoácidos , Sistemas de Transporte de Aminoácidos Neutros , Cromossomos Humanos Par 17/genética , Clonagem Molecular , Cosmídeos/genética , Éxons/genética , Saúde da Família , Feminino , Deleção de Genes , Expressão Gênica/genética , Marcadores Genéticos/genética , Vetores Genéticos/genética , Humanos , Masculino , Proteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras , Dados de Sequência Molecular , Linhagem , Mutação Puntual/genética , Mutação Puntual/fisiologia , Polimorfismo Conformacional de Fita Simples , Homologia de Sequência de AminoácidosRESUMO
Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.
Assuntos
Proteínas de Ciclo Celular , Clonagem Molecular/métodos , Proteínas de Ligação a DNA , Anemia de Fanconi/genética , Proteínas Nucleares , Proteínas/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Células Cultivadas , DNA Complementar , Anemia de Fanconi/patologia , Proteína do Grupo de Complementação C da Anemia de Fanconi , Proteínas de Grupos de Complementação da Anemia de Fanconi , Expressão Gênica , Teste de Complementação Genética , Humanos , Dados de Sequência Molecular , Mutação , Fases de Leitura Aberta , Biossíntese de Proteínas , Transcrição GênicaRESUMO
The fragile X syndrome is the most common cause of familial mental retardation. Genetic counseling and gene isolation are hampered by a lack of DNA markers close to the disease locus. Two somatic cell hybrids that each contain a human X chromosome with a breakpoint close to the fragile X locus have been characterized. A new DNA marker (DXS296) lies between the chromosome breakpoints and is the closest marker to the fragile X locus yet reported. The Hunter syndrome gene, which causes iduronate sulfatase deficiency, is located at the X chromosome breakpoint that is distal to this new marker, thus localizing the Hunter gene distal to the fragile X locus.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Ligação Genética , Marcadores Genéticos , Aberrações dos Cromossomos Sexuais/genética , Animais , Mapeamento Cromossômico , Feminino , Aconselhamento Genético , Biblioteca Genômica , Humanos , Células Híbridas , Funções Verossimilhança , Camundongos , Mucopolissacaridose II/genética , Mutação , Hibridização de Ácido Nucleico , Polimorfismo de Fragmento de Restrição , Translocação GenéticaRESUMO
Fragile sites are chemically induced nonstaining gaps in chromosomes. Different fragile sites vary in frequency in the population and in the chemistry of their induction. DNA sequences encompassing and including the rare, autosomal, folate-sensitive fragile site, FRA16A, were isolated by positional cloning. The molecular basis of FRA16A was found to be expansion of a normally polymorphic p(CCG)n repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The FRA16A locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis.
Assuntos
Fragilidade Cromossômica , Cromossomos Humanos Par 16 , Alelos , Sequência de Bases , Sítios Frágeis do Cromossomo , Cromossomos Artificiais de Levedura , Fosfatos de Dinucleosídeos/metabolismo , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Metilação , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Sequências Repetitivas de Ácido NucleicoAssuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Anemia de Fanconi/genética , Proteínas Nucleares , Proteínas/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA Complementar , Proteínas de Grupos de Complementação da Anemia de Fanconi , Expressão Gênica , Dados de Sequência MolecularRESUMO
Missense mutations in the TP53 tumor-suppressor gene inactivate its antitumorigenic properties and endow the incipient cells with newly acquired oncogenic properties that drive invasion and metastasis. Although the oncogenic effect of mutant p53 transcriptome has been widely acknowledged, the global influence of mutant p53 on cancer cell proteome remains to be fully elucidated. Here, we show that mutant p53 drives the release of invasive extracellular factors (the 'secretome') that facilitates the invasion of lung cancer cell lines. Proteomic characterization of the secretome from mutant p53-inducible H1299 human non-small cell lung cancer cell line discovered that the mutant p53 drives its oncogenic pathways through modulating the gene expression of numerous targets that are subsequently secreted from the cells. Of these genes, alpha-1 antitrypsin (A1AT) was identified as a critical effector of mutant p53 that drives invasion in vitro and in vivo, together with induction of epithelial-mesenchymal transition markers expression. Mutant p53 upregulated A1AT transcriptionally through the involvement with its family member p63. Conditioned medium containing secreted A1AT enhanced cell invasion, while an A1AT-blocking antibody attenuated the mutant p53-driven migration and invasion. Importantly, high A1AT expression correlated with increased tumor stage, elevated p53 staining and shorter overall survival in lung adenocarcinoma patients. Collectively, these findings suggest that A1AT is an indispensable target of mutant p53 with prognostic and therapeutic potential in mutant p53-expressing tumors.
Assuntos
Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/genética , alfa 1-Antitripsina/genética , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Mutação , Invasividade Neoplásica , Proteômica , Proteína Supressora de Tumor p53/fisiologia , Regulação para CimaRESUMO
Loss of heterozygosity on chromosomal arm 16q has been shown to be a frequent event in sporadic breast cancer and is suggested to be involved in cancer development through inactivation of a tumor-suppressor gene. To specify the commonly deleted region in which the unknown tumor-suppressor gene is located, a deletion map of chromosome 16 was constructed for 78 breast cancers, using 27 polymorphic DNA markers. Loss of heterozygosity on chromosome 16q was detected in 38 of the tumors. From the deletion map, the incidence of the loss of heterozygosity was deduced to be > or = 36% in the region distal to 16q12 and was most frequent in the 16q24.2-qter region. Then, association of the loss of heterozygosity in the 16q24.2-qter region with clinicopathological parameters of the tumors was examined for a total of 234 tumors, to reveal its biological significance in breast cancer development. The total incidence of loss of heterozygosity in the 16q24.2-qter region was 52% (118 of 225), and loss of heterozygosity was frequent irrespectively of the presence of invasion and metastasis, differences in clinical stage, tumor size, histological grade, or type, or amounts of estrogen receptor. Inactivation of an unknown tumor-suppressor gene on 16q24.2-qter was thus suggested to be involved commonly in the genesis of sporadic breast cancer, irrespectively of the extent of tumor spread or grade of aggressiveness of the cancer cells. On the other hand, eight cases revealed loss of heterozygosity not at 16q24-qter but in more proximal regions. Therefore, it appears that multiple tumor-suppressor genes are located on chromosome 16q.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Deleção Cromossômica , Mapeamento Cromossômico , Cromossomos Humanos Par 16 , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Genes Supressores de Tumor , Marcadores Genéticos , Humanos , Invasividade Neoplásica , Metástase Neoplásica , FenótipoRESUMO
Wilms' tumor (WT), a childhood cancer of the kidney, occurs in both familial and sporadic forms. Chromosome 11 genes have been implicated in the etiology of WT, and mutations in a gene at chromosomal band 11p13, WT1, have been identified in a few WT cases. However, 11p13 has been excluded as the site of the predisposition mutation segregating in several large WT families, which implies the existence of a non-11p familial predisposition gene. Recently, loss of heterozygosity for 16q markers located between chromosomal bands 16q13 and 16q22 has been reported in approximately 20% of sporadic Wilms' tumors. To determine if this region of 16q harbors the non-11p familial WT gene, a genetic linkage study of five WT families was undertaken. Using multipoint analyses, we ruled out genetic linkage of familial WT predisposition to 16q.
Assuntos
Cromossomos Humanos Par 16 , Genes do Tumor de Wilms , Neoplasias Renais/genética , Escore Lod , Tumor de Wilms/genética , Bandeamento Cromossômico , Feminino , Marcadores Genéticos , Humanos , Masculino , Linhagem , Polimorfismo de Fragmento de RestriçãoRESUMO
Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.
Assuntos
Neoplasias da Mama/genética , Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 16 , Perda de Heterozigosidade , Neoplasias da Mama/patologia , Fluorescência , Humanos , Radioisótopos de Fósforo , Reação em Cadeia da Polimerase/métodosRESUMO
This paper describes seven patients with ALL and a hypodiploid karyotype with less than 40 chromosomes. A consideration of these and 15 previously published cases indicates that they may be divided into two groups depending on chromosome number, i.e., less than 30 and 30-39. The less than 30 group are younger and predominantly female when compared with the 30-39 group, who are generally older than 40 years and mainly male. In addition, the two groups show different characteristic patterns of chromosome loss. Morphologically, both groups have populations of large and small lymphoblasts containing numerous small vacuoles, and both have common ALL antigen phenotypes. We present the possibility that the ALL patients in the less than 30 group are an example of an age restricted leukemia. There is insufficient data to assess any prognostic differences between the two patient groupings.
Assuntos
Aberrações Cromossômicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Cariotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , PrognósticoRESUMO
The gene for human leukemia inhibitory factor (LIF) has been mapped by Southern analysis of a series of mouse/human somatic cell hybrids and by in situ hybridization to the chromosomes of two normal males and some individuals with chromosomal rearrangements. The gene maps to 22q11-q12.2, between the Philadelphia translocation BCR gene and the breakpoint of the translocation in cell line GM2324 at 22q12.2. From the grain distribution over high resolution chromosome preparations, the most likely location is 22q12.1----q12.2. Southern analysis of DNA from one Ewing sarcoma with t[11;22][q24;q12] showed that the breakpoint on chromosome 22 is more than 15 kb 5' or 8 kb 3' from the LIF gene. The location of the LIF gene indicates that translocations of this gene are unlikely to play a role in myeloid leukemia and myeloproliferative disorders.
Assuntos
Cromossomos Humanos Par 22 , Inibidores do Crescimento/genética , Interleucina-6 , Linfocinas , Mapeamento por Restrição , Southern Blotting , Sondas de DNA , Rearranjo Gênico , Humanos , Fator Inibidor de Leucemia , Metáfase , Hibridização de Ácido Nucleico , Sarcoma de Ewing/genéticaRESUMO
Rearrangements involving chromosome 16, including inv(16) (p13q22), del(16)(q22), and t(16;16)(p13;q22), are frequent findings in acute myeloblastic leukemia (AML). Each of these rearrangements can occur as the sole karyotypic change or in association with additional chromosomal abnormalities, including in decreasing order of frequency: trisomy 22, trisomy 8, and deletion of the long arm of chromosome 7. We report a pediatric case of de novo AML, M4e subtype, with a unique combination of inv(16) (p13q22) and i(22q) occurring within the same leukemic clone. The inv(16) was detected by fluorescence in situ hybridization (FISH) analysis with two cosmid probes specific for sequences flanking the inv(16) breakpoint on the long arm of chromosome 16. Use of a chromosome-22-specific painting probe unequivocally identified a small metacentric chromosome as an i(22q). This case illustrates a variation in the association of trisomy 22 with inv(16) and suggests that duplication of the long arm of chromosome 22 may contain critical gene(s) involved in the multistep process of evolution of leukemia with 16q22 abnormalities.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 16/fisiologia , Cromossomos Humanos Par 22/fisiologia , Eosinofilia/genética , Leucemia Mielomonocítica Aguda/genética , Trissomia , Pré-Escolar , Marcadores Genéticos/genética , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , MetáfaseRESUMO
Pseudoxanthoma elasticum (PXE) is an inherited disorder of the elastic tissue with characteristic progressive calcification of elastic fibers in skin, eye, and the cardiovascular system. Recently mutations in the ABCC6 gene, encoding a transmembrane transporter protein, were identified as cause of the disease. Surprisingly, sequence and RFLP analysis for exon 9 with primers corresponding to flanking intronic sequence in diseased and haplotype negative members from all of our families and in a control population revealed either a homozygous or heterozygous state for the Q378X (1132C-->T) nonsense mutation in all individuals. With the publication of the genomic structure of the PXE locus we had identified the starting point of a large genomic segmental duplication within the locus in the cytogenetic interval defined by the Cy19 and Cy185 somatic cell hybrid breakpoints on chromosome 16p13.1. By means of somatic cell hybrid mapping we located this starting point telomeric to exon 10 of ABCC6. The duplication, however, does not include exon 10, but exons 1-9. These findings suggest that one or several copies of an ABCC6 pseudogene (psiABCC6) lie within this large segmental duplication. At least one copy contains exons 1-9 and maps to the chromosomal interval defined by the Cy163 and Cy11 breakpoints. Either this copy and/or an additional copy of psiABCC6 within Cy19-Cy183 carries the Q378X mutation that masks the correct identification of this nonsense mutation as being causative in pseudoxanthoma elasticum. Long-range PCR of exon 9 starting from sequence outside the genomic replication circumvents interference from the psiABCC6 DNA sequences and demonstrates that the Q378X mutation in the ABCC6 gene is associated with PXE in some families. These findings lead us to propose that gene conversion mechanisms from psiABCC6 to ABCC6 play a functional role in mutations causing PXE.
Assuntos
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Pseudogenes , Pseudoxantoma Elástico/genética , Alelos , Cromossomos Humanos Par 16 , Feminino , Conversão Gênica , Genótipo , Haplótipos , Humanos , Células Híbridas , Masculino , Modelos Genéticos , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Mapeamento por Restrição , Análise de Sequência de DNARESUMO
The chromosomal location of the gene encoding the human hair follicle protein trichohyalin has been determined by in situ hybridization. The human gene has been localized to the region 1q21.1-1q23 (probably 1q21.3) using a sheep trichohyalin cDNA probe. The genes encoding three other epithelial proteins, namely, profilaggrin, involucrin, and loricrin, are also located in the same region of chromosome 1, which, together with their similar gene and protein structures, suggests that the four proteins form a novel superfamily of epithelial structural proteins.
Assuntos
Proteínas de Filamentos Intermediários/genética , Proteínas de Membrana/genética , Precursores de Proteínas/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 1 , Proteínas Filagrinas , Humanos , Hibridização In Situ , Masculino , Metáfase , Homologia de Sequência do Ácido NucleicoRESUMO
11 beta-Hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) specifically modulates access of the mineralocorticoid aldosterone to the kidney mineralocorticoid type 1 receptors in a physiological environment in which there is a molar excess of cortisol. Cortisol and aldosterone have similar affinities for mineralocorticoid receptors. Mechanistically, 11 beta-HSD2 converts cortisol to cortisone. The other known isoform, 11 beta-HSD1, not only catalyzes the cortisol to cortisone reaction but also the reverse reaction, making it unlikely to play an important role in modulating the access of aldosterone to mineralocorticoid receptors. Mutations in the HSD11B2 gene (both exonic and intronic) have been demonstrated to cause reduced activity of this enzyme in the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive disorder. We hypothesized that this locus is also involved in the etiology of essential hypertension. To test this locus and flanking chromosomal regions for allelic association and genetic linkage to essential hypertension, it is necessary to have informative genetic markers. To this end, we have refined the localization of 11 beta-HSD2 to 16q22.1. We genotyped subjects using the nearest flanking microsatellites (D16S301 and D16S496). We conducted an association study using black subjects with hypertensive end-stage renal disease, black normotensive control subjects, and black and white individuals from the general population. We used chi 2 analysis and Fisher's exact test to test for association with these candidate gene markers. No significant association was found between D16S301 and hypertension. However, a positive association with hypertension was found at the D16S496 microsatellite locus (chi 2 = 6.98, df = 1, P < or = .008). Our data suggest that HSD11B2 is associated with hypertension in our black subjects with hypertensive end-stage renal disease. The 16q22.1 chromosome region potentially harbors a candidate gene for essential hypertension. Confirmation of our findings in another independently ascertained group of hypertensive subjects will provide a basis for proceeding with sib-pair linkage analyses.
Assuntos
População Negra/genética , Hidroxiesteroide Desidrogenases/genética , Hipertensão/etnologia , Hipertensão/genética , Isoenzimas/genética , Repetições de Microssatélites , 11-beta-Hidroxiesteroide Desidrogenases , Alelos , Sequência de Bases , Mapeamento Cromossômico , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sondas Moleculares/genética , Dados de Sequência Molecular , População BrancaRESUMO
The zincins are a superfamily of structurally-related Zn(2+)-binding metallopeptidases which play a major role in a wide range of biological processes including pattern formation, growth factor activation and extracellular matrix synthesis and degradation. In this paper we report the identification and complete primary structure of a novel 33 kDa protein which contains the zinc-binding HEXXH motif found in the zincin superfamily. We have named this novel protein PRSM1 (PRoteaSe, Metallo, number 1). The gene was identified by the immunoscreening of a human placental cDNA library using polyclonal antibodies raised to the 70 kDa human matrix metalloendopeptidase, type III procollagen N-proteinase [Halila, R. and Peltonen, L. (1986) Purification of human procollagen type III N-proteinase from placenta and preparation of antiserum. Biochem. J. 239, 47-52]. The protein is found in placenta and cultured osteosarcoma cells. PRSM1 could share sequence homology with the type III procollagen N-proteinase. The prsm1 gene is represented once in the human genome and is localized on chromosome 16 (q24.3).
Assuntos
Cromossomos Humanos Par 16 , Clonagem Molecular , Metaloendopeptidases/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
The molecular cytogenetic characterization and clinical details of 20 patients with marker chromosomes are presented. These 20 patients, together with another 22 patients previously published, represent a cohort in which the chromosomal origin of the marker chromosomes was successfully determined in all but one case. Examination of the pooled data suggests that the satellited markers derived from chromosomes 14, 15 (when metacentric or submetacentric), those whose origin is either 13 or 21, and those small ring autosomal markers derived from both alphoid and satellite II or III pericentric heterochromatin of chromosomes 1, 9, 15, and 16 are all associated with a low risk of phenotypic abnormality. The markers identified as i(18p), ring chromosomes derived from various autosomes, and satellited markers derived from chromosome 22 are associated with a high risk of phenotypic abnormality. The phenotype of patients with acrocentric markers derived from chromosome 15 was equivocal, perhaps as a result of imprinting. Additional data are required to confirm these trends. The mild mental retardation and abnormal face of a patient with a small ring chromosome derived from chromosome 4 are described. Identification of patients with small rings originating from particular chromosomes may allow the recognition of new syndromes.
Assuntos
Aberrações Cromossômicas/genética , Células Cultivadas , Aberrações Cromossômicas/patologia , Bandeamento Cromossômico , Transtornos Cromossômicos , Estudos de Coortes , Distamicinas , Feminino , Humanos , Indóis , Recém-Nascido , Cariotipagem , Linfócitos/patologia , Masculino , Fenótipo , Diagnóstico Pré-Natal , Coloração e RotulagemRESUMO
Here we report on a family with an inherited rearrangement of chromosome 8q, dir ins(8)(q24.11q13.3q21.13). Individuals with the chromosome abnormality, which does not appear to be associated with deletion of chromosome material, have manifestations of both tricho-rhino-phalangeal syndrome (TRPS) and branchio-oto syndrome (BOS). TRPS has been linked previously to deletions involving 8q24.11----q24.13, but none of the described patients with deletions in this part of 8q have had characteristics of the BOS. The presence of a breakpoint in 8q24.11 without apparent chromosome deletion in the family described suggests that TRPS maps to this band of 8q. Further, it is suggested that BOS maps to either 8q13.3 or 8q21.13.
Assuntos
Anormalidades Múltiplas/genética , Região Branquial/patologia , Aberrações Cromossômicas , Cromossomos Humanos Par 8 , Perda Auditiva/genética , Seios Paranasais/anormalidades , Anormalidades Múltiplas/patologia , Adulto , Pré-Escolar , Bandeamento Cromossômico , Mapeamento Cromossômico , Feminino , Rearranjo Gênico , Genes Recessivos , Humanos , Cariotipagem , Masculino , Linhagem , SíndromeRESUMO
We report on a 5-year-old boy with bilateral coloboma of iris, short stature, moderate developmental delay, and a few minor craniofacial anomalies. High-resolution GTG banding showed a small distal deletion of one chromosome 16 [del(16)(q23.1q24.2)]. Molecular refinement of the deletion breakpoints yielded that the proximal breakpoint at 16q23.1 is located between loci D16S395 (present) and D16S348 (absent). Comparison with previously published cases of deletion 16q demonstrated that the clinical phenotype is not a recognizable 16q- syndrome and different from the two cases of deletions of 16(q22.1 to q24.1) described by Callen et al. [1993]. Evidently, deletion 16(q23.1q24.2) has a milder phenotypic effect than other interstitial and distal 16q deletions.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Coloboma/genética , Anormalidades Craniofaciais/genética , Iris/anormalidades , Pré-Escolar , Bandeamento Cromossômico , Coloboma/patologia , Anormalidades Craniofaciais/patologia , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , MasculinoRESUMO
A new polymorphic DNA marker RN1, defining locus DXS369, was recently isolated. Using different somatic cell hybrids, RN1 was mapped between markers 4D-8 and U6.2. We have narrowed the localization of RN1 to the region between 4D-8 and FRAXA by genetic mapping in fragile X [fra(X)] families. Combined with information from other reports, the following order of loci on Xq27-q28 is suggested: cen-F9-(DXS105-DXS152)-DXS98-DXS369-FRAXA- DXS304-(DXS52-DXS15-F8)-tel. The locus DXS369 is closely linked to FRAXA, with a peak lodscore of 18.5 at a recombination fraction of 0.05. Therefore, RN1 is a useful probe for carrier detection and prenatal diagnosis in fra(X) families.