共查询到20条相似文献,搜索用时 15 毫秒
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Rodriguez-Revenga L Madrigal I Alkhalidi LS Armengol L González E Badenas C Estivill X Milà M 《American journal of medical genetics. Part A》2007,(9):916-920
Norrie disease (ND) is an X-linked disorder, inherited as a recessive trait that, therefore, mostly affects males. The gene responsible for ND, called NDP, maps to the short arm of chromosome X (Xp11.4-p11.3). We report here an atypical case of ND, consisting of a patient harboring a large submicroscopic deletion affecting not only the NDP gene but also the MAOA, MAOB, and EFHC2 genes. Microarray comparative genomic hybridization (CGH) analysis showed that 11 consecutive bacterial artificial chromosome (BAC) clones, mapping around the NDP gene, were deleted. These clones span a region of about 1 Mb on Xp11.3. The deletion was ascertained by fluorescent in situ hybridization (FISH) analysis with different BAC clones located within the region. Clinical features of the proband include bilateral retinal detachment, microcephaly, severe psychomotor retardation without verbal language skills acquired, and epilepsy. The identification and molecular characterization of this case reinforces the idea of a new contiguous gene syndrome that would explain the complex phenotype shared by atypical ND patients. 相似文献
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WDR45B‐related intellectual disability,spastic quadriplegia,epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome 下载免费PDF全文
J. Suleiman D. Allingham‐Hawkins M. Hashem H.E. Shamseldin F.S. Alkuraya A.W. El‐Hattab 《Clinical genetics》2018,93(2):360-364
The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early‐onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease. 相似文献
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Macrocerebellum,epilepsy, intellectual disability,and gut malrotation in a child with a 16q24.1–q24.2 contiguous gene deletion 下载免费PDF全文
Andrea H. Seeley Mark A. Durham Mark A. Micale Jeffrey Wesolowski Bradley R. Foerster Donna M. Martin 《American journal of medical genetics. Part A》2014,164(8):2062-2068
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Cerebral palsy,epilepsy, and severe intellectual disability in a patient with 3q29 microduplication syndrome 下载免费PDF全文
Alberto Fernández‐Jaén María del Carmen Castellanos Ana Laura Fernández‐Perrone Daniel Martín Fernández‐Mayoralas Alberto González de la Vega Beatriz Calleja‐Pérez Ester Corbacho Fernández Jacobo Albert María Carmen Sánchez Hombre 《American journal of medical genetics. Part A》2014,164(8):2043-2047
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Loss of the SHOX gene associated with Leri-Weill dyschondrosteosis in a 45,X male 总被引:1,自引:0,他引:1 下载免费PDF全文
L Stuppia G Calabrese P Borrelli V Gatta E Morizio R Mingarelli G Di A Crino A Giannotti G Rappold G Palka 《Journal of medical genetics》1999,36(9):711-713
A male patient is reported with a 45,X karyotype and Leri-Weill dyschondrosteosis (LWD). FISH analysis with SHOX and SRY gene probes was carried out. One copy of both SHOX and SRY was detected in interphase nuclei, clarifying the origin of LWD and the male phenotype. Molecular results suggested that the 45,X karyotype arose through two independent events. The first occurred at paternal meiosis leading to an unequal crossing over between the short arms of the X and Y chromosomes. As a consequence, the SRY gene was translocated onto Xp, thereby explaining the male phenotype of the patient. The second event probably occurred at maternal meiosis or at the early stages of the zygote resulting in the loss of the maternal X chromosome. 相似文献
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Mégarbané A 《American journal of medical genetics. Part A》2003,(4):381-384
We report two male cousins with short stature, microcephaly, hypertelorism, optic atrophy, ptosis, absent ear lobes, high-arched palates, abnormal EEG, and severe mental retardation. Both cousins have consanguineous parents. Differential diagnoses are discussed and the possibility that we might be reporting on a new syndrome is raised. 相似文献
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Yang Y Beyer BJ Otto JF O'Brien TP Letts VA White HS Frankel WN 《Human molecular genetics》2003,12(9):975-984
The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. Despite its clinical relevance, the potential of ECT to identify mouse epilepsy models in genetic studies has not been thoroughly assessed. We adopted the ECT test to screen the progeny of ethylnitrosourea treated male C57BL/6J mice. In a small-scale screen, several mutant lines conferring a low threshold to ECT minimal clonic seizures were mapped to the telomeric region of mouse chromosome 2 in independent founder families. This high incidence was suggestive of a single spontaneous event that pre-existed in the founders of mutagenized stock. Genetic and physical mapping led to the discovery that several lines shared a single mutation, Szt1 (seizure threshold-1), consisting of a 300 kb deletion of genomic DNA involving three known genes. Two of these genes, Kcnq2 and Chrna4, are known to be mutated in human epilepsy families. Szt1 homozygotes and heterozygotes display similar phenotypes to those found in the respective Kcnq2 knockout mutant mice, suggesting that Kcnq2 haploinsufficiency is at the root of the Szt1 seizure sensitivity. Our results provide a novel genetic model for epilepsy research and demonstrate that the approach of using ECT to study seizures in mice has the potential to lead to the identification of human epilepsy susceptibility genes. 相似文献
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Valetto A Orsini A Bertini V Toschi B Bonuccelli A Simi F Sammartino I Taddeucci G Simi P Saggese G 《European journal of medical genetics》2012,55(5):362-366
We report on a de novo interstitial deletion of chromosome 21q in a patient presenting with characteristic facial features, intellectual disability, and epilepsy. The deletion extent was about 4.9 Mb from position 37713441 bp (21q22.13) to position 42665162 bp (21q22.3) (NCBI36/hg18 map).Patients with partial monosomy 21 are quite rare; this anomaly has been associated with a wide spectrum of clinical signs, ranging from very mild to quite severe phenotypes. This variability results from variability in the deleted regions, thus accurate molecular definition of the chromosomal breakpoints is necessary to make better genotype-phenotype correlations.We compared our patient's phenotype with the few other patients reported in the literature and found to have similar deletion when analyzed by array CGH. The minimal overlapping region contains only two genes, DYRK1A and KCNJ6, which may play a major role in these patients' phenotype. 相似文献
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Tzschach A Grasshoff U Schäferhoff K Bonin M Dufke A Wolff M Haas-Lude K Bevot A Riess O 《American journal of medical genetics. Part A》2012,(7):1709-1712
Interstitial deletions of chromosome bands 9q34.11-q34.13 are rare. We report on a 16-year-old female patient with severe intellectual disability, congenital hydrocephalus, cleft lip and palate, talipes equinovarus, epilepsy, kyphoscoliosis, convergent strabismus, severe short stature, dystrophy, and facial dysmorphic signs. Array analysis revealed a 3.7?Mb interstitial deletion in 9q34.11-q34.13. The deletion harbors more than 60 genes, including SPTAN1, DYT1/TOR1A, ABL1, ASS1, LAMC3, POMT1, DOLK, and GLE1, mutations in which have previously been associated with monogenic disorders. This is the first patient with a deletion of this size and position in 9q34.11-q34.13. Reports of additional patients with aberrations in this region will be needed to establish karyotype-phenotype correlations and to gain information on the contribution of individual genes for the clinical manifestations. 相似文献
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Two clinically distinct disorders, Wolman disease (WD) and cholesteryl ester storage disease (CESD), are allelic autosomal recessive disorders caused by different mutations in lysosomal acid lipase (LIPA) which encodes for an essential enzyme involved in the hydrolysis of intracellular cholesteryl esters and triglycerides. We describe a case of lysosomal acid lipase deficiency in an infant with WD and report on a novel mutation type, intragenic deletion. 相似文献
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Leda Paganini Loubna A. Hadi Massimiliano Chetta Davide Rovina Laura Fontana Patrizia Colapietro Eleonora Bonaparte Lidia Pezzani Paola Marchisio Silvia M. Tabano Jole Costanza Silvia M. Sirchia Laura Riboni Donatella Milani Monica Miozzo 《Clinical genetics》2019,95(3):368-374
X-linked intellectual disability (XLID) refers to a clinically and genetically heterogeneous neurodevelopmental disorder, in which males are more heavily affected than females. Among the syndromic forms of XLID, identified by additional clinical signs as part of the disease spectrum, the association between XLID and severe myopia has been poorly characterized. We used whole exome sequencing (WES) to study two Italian male twins presenting impaired intellectual function and adaptive behavior, in association with severe myopia and mild facial dysmorphisms. WES analysis detected the novel, maternally inherited, mutation c.916G > C (G306R) in the X-linked heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) gene. HS6ST2 transfers sulfate from adenosine 3′-phosphate, 5′-phosphosulfate to the sixth position of the N-sulphoglucosamine residue in heparan sulfate (HS) proteoglycans. Low HS sulfation levels are associated with defective optic disc and stalk morphogenesis during mammalian visual system development. The c.916G>C variant affects the HS6ST2 substrate binding site, and its effect was considered “deleterious” by in-silico tools. An in-vitro enzymatic assay showed that the HS6ST2 mutant isoform had significantly reduced sulphotransferase activity. Taken together, the results suggest that mutant HS6ST2 is possibly involved in the development of myopia and cognitive impairment, characteristics of the probands reported here. 相似文献
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Raquel M Fernández Rocío Nú?ez-Torres Antonio González-Meneses Guillermo Anti?olo Salud Borrego 《BMC medical genetics》2010,11(1):137
Background
Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes. 相似文献18.
Badens C Lacoste C Philip N Martini N Courrier S Giuliano F Verloes A Munnich A Leheup B Burglen L Odent S Van Esch H Levy N 《Clinical genetics》2006,70(1):57-62
Mutations in ATRX are associated with a wide and clinically heterogeneous spectrum of X-linked mental retardation syndromes. The ATRX protein, involved in chromatin remodelling, belongs to the family of SWI/SNF DNA helicases and contains a plant homeodomain (PHD)-like domain. To date, more than 60 different mutations have been reported in ATRX. One of them is recurrent and accounts for 20% of all the reported mutations, whereas all others are private. Most mutations are clustered in the two major functional domains, the helicase and the PHD-like domain. So far, no clear genotype-phenotype correlation has been established, with exception to the rare truncating mutations located at the C-terminal part of the protein, which are consistently associated with severe urogenital defects. In this study, we report the molecular analysis performed in 16 families positive for ATRX. Our findings indicate that, in addition to the previously described mutation 'hotspot' in the PHD-like domain, two other protein sections emerge as minor 'hotspots' in the helicase region encoded by exons 18-20 and 26-29, respectively, gathering 33% of all described mutations. Additionally, based on the clinical data collected for 22 patients from the 16 families, we observe that mutations in the PHD-like domain produce severe and permanent psychomotor deficiency, usually preventing patients from walking, as well as constant urogenital abnormalities, while mutations in the helicase domain lead to delayed but correct psychomotor acquisitions together with mild or absent urogenital abnormalities. In summary, mutations in the helicase domain are associated with milder phenotypes than mutations in the PHD-like domain. 相似文献
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Zhang Y Malekpour M Al-Madani N Kahrizi K Zanganeh M Lohr NJ Mohseni M Mojahedi F Daneshi A Najmabadi H Smith RJ 《Journal of medical genetics》2007,44(4):233-240