RESUMO
Silver-Russell syndrome (SRS) is a growth retardation syndrome characterized by intrauterine and postnatal growth retardation, relative macrocephaly and protruding forehead, body asymmetry and feeding difficulties. Nearly 50% of cases show a hypomethylation in 11p15.5, in 10% maternal uniparental disomy of chromosome 7 is present. A significant number of patients with SRS features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for SRS genetic testing by molecular karyotyping. Pathogenic variants could be detected in five of them, including a NSD1 duplication in 5q35 and a 14q32 microdeletion. NSD1 deletions are detectable in overgrowth disorders (Sotos syndrome and Beckwith-Wiedemann syndrome), whereas NSD1 duplications are associated with growth retardation. The 14q32 deletion is typically associated with Temple syndrome (TS14), but the identification of a patient in our cohort reflects the clinical overlap between TS14 and SRS. As determination of molecular subtypes is the basis for a directed counseling and therapy, the identification of pathogenic variants in >10% of the total cohort of patients referred for SRS testing and in >16% of characteristic individuals with the characteristic SRS phenotype confirms the need to apply molecular karyotyping in this cohort.
Assuntos
Cromossomos Humanos Par 5/genética , Duplicação Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Síndrome de Silver-Russell/genética , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Estudos de Coortes , Feminino , Testes Genéticos , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Recém-Nascido , Cariotipagem , Masculino , Fenótipo , Síndrome de Silver-Russell/diagnósticoRESUMO
Anorectal malformations (ARM) encompass a broad clinical spectrum which ranges from mild anal stenosis to severe anorectal anomalies such as complex cloacal malformations. The overall incidence of ARM is around 1 in every 2,500 live births. Although causative genes for a few syndromic forms have been identified, the molecular genetic background of most ARM remains unknown. The present report describes a patient with a de novo 13.2-Mb deletion of chromosome 18q22.3-qter and a 2.2-Mb de novo duplication of chromosomal region 18pter-p11.32 located at the telomeric end of chromosome 18q. The patient presented with ARM and the typical features of 18q- syndrome (De-Grouchy syndrome). The combination of a partial duplication of the short arm and a partial deletion of the long arm of chromosome 18 has been described in 16 previous cases. However, this is the first report of an association between this complex chromosomal rearrangement and ARM.
Assuntos
Canal Anal/anormalidades , Cromossomos Humanos Par 18 , Reto/anormalidades , Trissomia , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariotipagem , MasculinoRESUMO
Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders with a significant clinical overlap. The recent discovery of heterozygous mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC and CS suggested a similar underlying pathogenesis of these two disorders. While CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS alterations are almost exclusively associated with CS. We carried out a comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals with CS. Twelve different BRAF alterations were found in twenty-four patients with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence variations in three CFC-affected individuals (5.9%), whereas three patients had a KRAS alteration (5.9%). We identified four different missense mutations of HRAS in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two infants with a phenotype meeting criteria for CS (6.5%). In 14 informative families, we traced the parental origin of HRAS alterations and demonstrated inheritance of the mutated allele exclusively from the father, further confirming a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence of slight phenotypic differences regarding craniofacial features in MAP2K1- and MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype correlations.
Assuntos
Anormalidades Múltiplas/genética , Fácies , Cardiopatias Congênitas/genética , Mutação , Anormalidades da Pele/genética , Adulto , Criança , Análise Mutacional de DNA , Deficiências do Desenvolvimento , Humanos , Deficiência Intelectual , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 2/genética , Fenótipo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Síndrome , Proteínas ras/genéticaRESUMO
BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). CONCLUSIONS: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.
Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Deleção Cromossômica , Neoplasias Gastrointestinais/genética , Polipose Intestinal/genética , Síndromes Neoplásicas Hereditárias/genética , PTEN Fosfo-Hidrolase/genética , Proteína Smad4/genética , Adolescente , Adulto , Idade de Início , Antígenos CD , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/deficiência , Caderinas/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Neoplasias Gastrointestinais/epidemiologia , Heterogeneidade Genética , Genótipo , Alemanha/epidemiologia , Humanos , Lactente , Polipose Intestinal/epidemiologia , Masculino , Síndromes Neoplásicas Hereditárias/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , PTEN Fosfo-Hidrolase/deficiência , Fenótipo , Mutação Puntual , Proteína Smad4/deficiência , Telangiectasia Hemorrágica Hereditária/epidemiologia , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
BACKGROUND: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. METHODS: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. RESULTS: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. CONCLUSION: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Córtex Cerebral/anormalidades , Predisposição Genética para Doença/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Malformações do Sistema Nervoso/genética , Adolescente , Adulto , Movimento Celular/genética , Cerebelo/anormalidades , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Coristoma/genética , Coristoma/metabolismo , Análise Mutacional de DNA , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Lactente , Masculino , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Penetrância , FenótipoRESUMO
Cohen syndrome (CS) is an autosomal recessive disorder with variability in the clinical manifestations, characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in the gene COH1 have been found in an ethnically diverse series of patients. Brief clinical descriptions of 24 patients with CS are provided. The patients were from 16 families of different ethnic backgrounds and between 2.5 and 60 years of age at assessment. DNA samples from all patients were analysed for mutations in COH1 by direct sequencing. Splice site mutations were characterised using reverse transcriptase PCR analysis from total RNA samples. In this series, we detected 25 different COH1 mutations; 19 of these were novel, including 9 nonsense mutations, 8 frameshift mutations, 4 verified splice site mutations, 3 larger in frame deletions, and 1 missense mutation. We observed marked variability of developmental and growth parameters. The typical facial gestalt was seen in 23/24 patients. Early onset progressive myopia was present in all the patients older than 5 years. Widespread pigmentary retinopathy was found in 12/14 patients assessed over 5 years of age. We present evidence for extended allelic heterogeneity of CS, with the vast majority of mutations leading to premature termination codons in COH1. Our data confirm the broad clinical spectrum of CS with some patients lacking even the characteristic facial gestalt and pigmentary retinopathy at school age.
Assuntos
Anormalidades Múltiplas/diagnóstico , Deficiência Intelectual/diagnóstico , Proteínas de Membrana/genética , Miopia/diagnóstico , Retinose Pigmentar/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Face/anormalidades , Feminino , Heterogeneidade Genética , Humanos , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Mutação , Miopia/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Retinose Pigmentar/genética , Síndrome , Proteínas de Transporte VesicularAssuntos
Braço/anormalidades , Cardiopatias Congênitas/genética , Proteínas com Domínio T/genética , Adolescente , Adulto , Pré-Escolar , Cromossomos Humanos Par 12/genética , DNA/análise , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Fenótipo , Análise de Sequência de DNA/métodos , SíndromeRESUMO
An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Ataxias Espinocerebelares/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Expansão das Repetições de Trinucleotídeos , Adulto , Idade de Início , Demência/complicações , Demência/genética , Feminino , Homozigoto , Humanos , Repetições de Microssatélites , Fatores de Iniciação de Peptídeos/genética , Peptídeos/genéticaRESUMO
We present three patients with congenital generalized lipodystrophy, sensorineural deafness, low birth weight, short stature, delayed cognitive development, and progressive bone changes characterized by overtubulation and rarefaction of long bones with dense metaphyseal striations occurring in adolescence. Abnormalities of lipid and carbohydrate metabolism, hepatosplenomegaly, acanthosis nigricans, and hirsutism were not found. Comparison of the condition of these patients with known syndromic lipodystrophies suggests that they represent a previously unrecognized genetic disorder. The occurrence in sibs born to consanguineous parents and a third patient from the same tribal unit suggest autosomal recessive inheritance.
Assuntos
Doenças Ósseas/congênito , Surdez/congênito , Nanismo/genética , Deficiência Intelectual/genética , Lipodistrofia/congênito , Adolescente , Adulto , Doenças Ósseas/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Radiografia , SíndromeRESUMO
X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.
Assuntos
Encefalopatias/genética , Coristoma/genética , Proteínas Associadas aos Microtúbulos , Mosaicismo/diagnóstico , Malformações do Sistema Nervoso/genética , Neuropeptídeos/genética , Penetrância , Adulto , Encefalopatias/complicações , Encefalopatias/diagnóstico , Movimento Celular/genética , Criança , Coristoma/complicações , Coristoma/diagnóstico , Cromossomos Humanos X/genética , Análise Mutacional de DNA , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Éxons , Feminino , Heterozigoto , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Mutação , Malformações do Sistema Nervoso/complicações , Malformações do Sistema Nervoso/diagnóstico , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita Simples , Fatores SexuaisRESUMO
Paternal uniparental disomy (UPD) of chromosome 6 has been reported several times in patients with (transient) neonatal diabetes mellitus ((T)NDM). Here we present our short tandem repeat typing results in a new patient with NDM, revealing a paternal isodisomy (UPiD). Summarising these data with those published previously on complete paternal (n=13) and maternal (n=2) UPD6, all cases show isodisomy. In general, several modes of UPD formation have been suggested: While a meiotic origin of UPD mainly results in a uniparental heterodisomy (UPhD), UPiD is probably the result of a post-zygotic mitotic error. This mode of formation consists of a mitotic nondisjunction in a disomic zygote, followed by either a trisomic rescue or a reduplication. Endoduplication in a monosomic zygote is another possible but less probable mechanism, taking into consideration that monosomic zygotes are not viable. The exclusive finding of isodisomy in case of chromosome 6 therefore gives strong evidence that segregational errors of this chromosome are mainly influenced by postzygotic factors. This hypothesis is supported by the observation of two cases with partial paternal UPiD6 originating from mitotic recombination events. The influence of mitotic segregational errors in UPD6 formation is in agreement with the results in trisomy/UPD of other chromosomes of the C group (7 and 8), and is in remarkable contrast to the findings in studies on the origin of the frequent aneuploidies. Multiple factors ensure normal segregation and we speculate that they vary in importance for each chromosome.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Diabetes Mellitus/congênito , Diabetes Mellitus/genética , Macroglossia/genética , Ploidias , Mapeamento Cromossômico , Feminino , Impressão Genômica , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Zigoto/fisiologiaRESUMO
OBJECTIVE: Models of bulimia lack a clear conceptualization of avoidance. This study considers the role of different domains of schema avoidance in bulimic disorders and examines the association of scores on the Young-Rygh Avoidance Inventory (YRAI) with bulimic pathology. METHODS: A total of 19 bulimic and 74 comparison women completed the YRAI and a measure of bulimic psychopathology. RESULTS: Bulimics scored significantly higher than the nonclinical women did on all YRAI scales. Greater reported use of avoidance was positively associated with bulimic attitudes, but only among the comparison group. At a dimensional level, behavioral/somatic avoidance was more strongly associated with bulimic pathology than cognitive/emotional avoidance, but the same was not true when differentiating groups. CONCLUSIONS: The YRAI is a robust measure of different domains of schema avoidance in understanding bulimic psychopathology. Clinically, the YRAI might be used to guide treatment for bulimic disorders.
Assuntos
Bulimia/psicologia , Transtornos da Personalidade/psicologia , Adolescente , Adulto , Bulimia/diagnóstico , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
PURPOSE: Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 x 1.0 Gy versus 5 x 0.5 Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 x 1.0 Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 x 1.0 Gy; group 4, 5 x 0.5 Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively. RESULTS: Local irradiation of non-arthritic rats (group 1) with 5 x 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 x 1 Gy (group 3) or 5 x 0.5 Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29--group 3: p=0.037; group 4: p=0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29--group 3: p=0.0036; group 4: p=0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p=0.015; group 4: p=0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups. CONCLUSIONS: This study confirms by objective criteria the anti-inflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.
Assuntos
Artrite Experimental/radioterapia , Animais , Artrite Experimental/microbiologia , Artrite Experimental/fisiopatologia , Feminino , Mycobacterium tuberculosis , Dosagem Radioterapêutica , Ratos , Ratos Endogâmicos LewRESUMO
Constitutional interstitial deletions of 5q are uncommon. The corresponding phenotype is not well defined. But severe mental retardation seems to be a consistent manifestation. We describe a 4-year-old girl with a de novo deletion of 5q33.3q35.1 presenting only with mild psychomotor delay, minor facial anomalies, and seizures.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Deficiência Intelectual/genética , Adulto , Pré-Escolar , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/patologia , Cariotipagem , MasculinoRESUMO
Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.
Assuntos
Cromossomos Humanos Par 4/genética , Disostoses/genética , Síndrome de Ellis-Van Creveld/genética , Etnicidade/genética , Genes , Proteínas de Membrana/genética , Anormalidades Dentárias/genética , Processamento Alternativo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Brasil/epidemiologia , Mapeamento Cromossômico , Nanismo/genética , Síndrome de Ellis-Van Creveld/etnologia , Etiquetas de Sequências Expressas , Feminino , Dedos/anormalidades , Genes Dominantes , Cardiopatias Congênitas/genética , Heterozigoto , Humanos , Incisivo/anormalidades , Zíper de Leucina/genética , Masculino , Proteínas de Membrana/fisiologia , Repetições de Microssatélites , Dados de Sequência Molecular , Linhagem , Pennsylvania/epidemiologia , Fenótipo , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Proteínas , Recombinação Genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SíndromeRESUMO
Léri-Weill syndrome (LWS) or dyschondrosteosis represents a short stature syndrome characterised by the mesomelic shortening of the forearms and lower legs and by bilateral Madelung deformity of the wrists. Recently, mutations in the pseudoautosomal homeobox gene SHOX have been shown to be causative for this disorder. This gene has previously been described as the short stature gene implicated in Turner syndrome (TS). We studied 32 Léri-Weill patients from 18 different German and Dutch families and present clinical, radiological and molecular data. Phenotypic inter- and intrafamilial heterogeneity is a frequent finding in LWS, and phenotypic manifestations are generally more severe in females. In males, muscular hypertrophy is a frequent finding. To test for SHOX mutations we used FISH, Southern blot and SSCP analysis as well as long-range PCR and sequencing. We identified (sub)microscopic deletions encompassing the SHOX gene region in 10 out of 18 families investigated. Deletion sizes varied between 100 kb and 9 Mb and did not correlate with the severity of the phenotype. We did not detect SHOX mutations in almost half (41%) the LWS families studied, which suggests different genetic etiologies.
Assuntos
Proteínas de Homeodomínio/genética , Osteocondrodisplasias/genética , Adolescente , Adulto , Southern Blotting , Estatura/genética , Osso e Ossos/diagnóstico por imagem , Criança , Deleção Cromossômica , Análise Mutacional de DNA , Feminino , Antebraço/diagnóstico por imagem , Variação Genética , Humanos , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteocondrodisplasias/diagnóstico por imagem , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Radiografia , Deleção de Sequência , Cromossomos Sexuais/genética , Proteína de Homoeobox de Baixa Estatura , SíndromeAssuntos
Cardiopatias Congênitas/genética , Deformidades Congênitas dos Membros/genética , Mutação/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 12/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Testes Genéticos , Variação Genética/genética , Genótipo , Bloqueio Cardíaco/genética , Defeitos dos Septos Cardíacos/genética , Humanos , Íntrons/genética , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita Simples , Sindactilia/genética , SíndromeRESUMO
We report a case of postnatal onset short stature and a distinctive pitted enamel hypoplasia in a 19-year-old woman. Growth hormone deficiency and other endocrine deficiencies were excluded. Additional observations of similar cases might outline a newly recognized syndrome.
Assuntos
Estatura , Hipoplasia do Esmalte Dentário/genética , Adulto , Osso e Ossos/patologia , Feminino , HumanosRESUMO
We report on a mother and her 5-year old son, both with a terminal deletion of the short arm of the X chromosome. By molecular genetic analysis the breakpoint was located distal to steroid sulfatase gene. The boy manifested, due to nullisomy of this region, short stature (SHOX), chondrodysplasia punctata (ARSE), and mental retardation (putative mental retardation gene MRX 49). Short stature is present in mother and son, but both also had bilateral Madelung deformity, a key finding in the Léri-Weill syndrome. We discuss the phenotype in relationship to hitherto published cases with chromosomal aberrations and contiguous gene syndromes of Xp22.3.