排序方式: 共有145条查询结果,搜索用时 15 毫秒
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Shaheen R Faqeih E Seidahmed MZ Sunker A Alali FE AlQahtani K Alkuraya FS 《Human mutation》2011,32(6):573-578
Meckel Gruber syndrome (MKS) is an autosomal recessive multisystem disorder that represents a severe form of ciliopathy in humans and is characterized by significant genetic heterogeneity. In this article, we describe the identification of a novel MKS locus MKS8 that we map to TCTN2, in a multiplex consanguineous family. TCTN2 is a paralog of the recently identified Tectonic 1, which has been shown to modulate sonic hedgehog signaling. Expression analysis at different developmental stages of the murine ortholog revealed a spatial and temporal pattern consistent with the MKS phenotype observed in our patient. The exclusion of this and the other seven MKS genes in our collection of consanguineous Arab MKS families confirms the existence of two additional MKS loci. 相似文献
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Alkuraya FS 《American journal of medical genetics. Part A》2011,155(2):297-300
In this article, the unusual combination of arthrogryposis, upward gaze palsy, and Perthes disease in two sisters and their cousin who are all part of an extended consanguineous Saudi family is reported. All patients had difficult to control bronchial asthma and subtle facial dysmorphism. Two of the three had pyloric stenosis, two were intellectually normal, and one had academic problems but had a history of birth hypoxia. Pedigree is consistent with an autosomal recessive mode of inheritance. Lack of previous reports suggests this represents a novel syndromic form of arthrogryposis. 相似文献
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Almaghlouth IA Mohamed JY Al-Amoudi M Al-Ahaidib L Al-Odaib A Alkuraya FS 《Clinical genetics》2012,82(2):193-196
Gamma-glutamyl cycle is a six-enzyme cycle that represents the primary pathway for glutathione synthesis and degradation. 5-Oxoprolinase deficiency is an extremely rare disorder of the gamma-glutamyl cycle with only eight patients reported to date. Debate continues as to whether this is a benign biochemical defect because of the heterogeneity of the clinical presentation which ranges from normal to significant neurological involvement. Here, we report the first molecularly characterized patients with 5-oxoprolinase deficiency due to a mutation in OPLAH (which encodes 5-oxoprolinase). The largely benign clinical course of the patients described herein despite persistent 5-oxoprolinuria highlights the importance of establishing a molecular diagnosis in the few cases with abnormal neurological outcome to exclude potentially overlapping biochemical defects and to explore potential genotype/phenotype correlation. 相似文献
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Background Fanconi anaemia (FA) is a group of disorders characterised by progressive bone marrow failure and a characteristic but variable craniofacial and skeletal involvement. Recessive mutations in any of 15 genes linked to FA lead to the pathognomonic increased susceptibility to double-strand DNA breaks. Methods Autozygome and exome analysis of a patient with classic FA phenotype Results The authors identified a novel truncating mutation in XRCC2. Consistent with the proposed causal link to FA, this gene is an essential non-redundant component of the RAD51 family of homologous repair proteins and its deficiency in a murine model has been shown to lead to a highly similar phenotype to that of this patient both at the cellular and organismal level. Conclusion This study implicates XRCC2 in the pathogenesis of FA and calls for further investigation of the potential contribution of XRCC2 mutations to the overall mutational load of FA. 相似文献
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Abubakar Moawia MSc Ranad Shaheen PhD Sajida Rasool MSc Syeda Seema Waseem MSc Nour Ewida BSc Birgit Budde PhD Amit Kawalia PhD Susanne Motameny PhD Kamal Khan MSc Ambrin Fatima PhD Muhammad Jameel PhD Farid Ullah MSc Talia Akram MSc Zafar Ali MSc Uzma Abdullah MSc Saba Irshad PhD Wolfgang Höhne PhD Angelika Anna Noegel PhD Mohammed Al‐Owain MD Konstanze Hörtnagel MD Petra Stöbe ScD Shahid Mahmood Baig PhD Peter Nürnberg PhD Fowzan Sami Alkuraya MD Andreas Hahn MD Muhammad Sajid Hussain PhD 《Annals of neurology》2017,82(4):562-577
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Anselm IA Anselm IM Alkuraya FS Salomons GS Jakobs C Fulton AB Mazumdar M Rivkin M Frye R Poussaint TY Marsden D 《Journal of inherited metabolic disease》2006,29(1):214-219
Summary We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those
previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation,
absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic
features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on
brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation
and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of
the 3′ end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum
of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.
First and second author contributed equally to this paper
Communicating editor: Michael Gibson
Competing interests: None declared
An erratum to this article is available at . 相似文献
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Arif O. Khan Nisha Patel Nicola G. Ghazi Shahad S. Alzahrani Stefan T. Arold Fowzan S. Alkuraya 《Ophthalmic genetics》2018,39(5):577-583
Purpose: The purpose of this study is to uncover the genetic cause for non-syndromic macular “coloboma” (pseudocoloboma) in three brothers from a consanguineous family.Methods: Homozygosity mapping for the three affected brothers and whole-exome sequencing in one affected brother, followed by confirmatory Sanger sequencing and segregation analysis of the candidate gene for all immediate family members; molecular modeling of the candidate mutation; and review of clinical, imaging, and laboratory findings.Results: Three otherwise-healthy brothers (age 10, 10, and 6 years) had macular pseudocoloboma. Both parents and the fourth brother were not affected. Parents were first cousins. A novel homozygous missense variant in claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated with the phenotype, and molecular modeling predicts an unfavorable effect to protein function. All prior reported biallelic CLND19 mutations cause symptomatic hypomagnesemia with hypercalciuria and nephrocalcinosis, often with concurrent macular pseudocoloboma. However, general physical assessment, metabolic profile, and renal imaging for the three affected brothers were normal.Conclusions: A homozygous CLDN19 mutation can cause macular pseudocoloboma without evidence for systemic disease in children. This is the first reported family with CLDN19 mutations to have an ocular phenotype only; however, those identified to harbor biallelic CLDN19 mutations should be considered at risk for the extraocular manifestations that have previously been associated with mutations in the gene. 相似文献