Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3

Kahrizi, Kimia; Hu, Cougar Hao; Garshasbi, Masoud; Abedini, Seyedeh Sedigheh; Ghadami, Shirin; Kariminejad, Ariana; Ullmann, Reinhard; Chen, Wei; Ropers, Hans‐Hilger; Kuß, Andreas W.; Najmabadi, Hossein; Tzschach, Andreas

doi:10.1038/ejhg.2010.132

Cited by 56 publications

(49 citation statements)

References 7 publications

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“…Their conclusions were based foremost on mutations in SRD5A3 in a large Emirati family from Baluchi (Southern Iran) and children from seven other families. Subsequently, other studies also identified mutations in patients further supporting SRD5A3 as associated with CDGs (Gründahl et al, 2012;Kahrizi et al, 2011;Kasapkara et al, 2012;Morava et al, 2010). Interestingly, these patients exhibited residual dolichol levels, implying that there must be an alternative pathway for dolichol biosynthesis Gründahl et al, 2012).…”

Section: Biosynthesis Of the Eukaryotic Dolichyl Lipid Carriersmentioning

confidence: 99%

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Bickford

Nick

2013

Microbiology

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Isoprenoid lipid carriers are essential in protein glycosylation and bacterial cell envelope biosynthesis. The enzymes involved in their metabolism (synthases, kinases and phosphatases) are therefore critical to cell viability. In this review, we focus on two broad groups of isoprenoid pyrophosphate phosphatases. One group, containing phosphatidic acid phosphatase motifs, includes the eukaryotic dolichyl pyrophosphate phosphatases and proposed recycling bacterial undecaprenol pyrophosphate phosphatases, PgpB, YbjB and YeiU/LpxT. The second group comprises the bacterial undecaprenol pyrophosphate phosphatase, BacA/UppP, responsible for initial formation of undecaprenyl phosphate, which we predict contains a tyrosine phosphate phosphatase motif resembling that of the tumour suppressor, phosphatase and tensin homologue (PTEN). Based on protein sequence alignments across species and 2D structure predictions, we propose catalytic and lipid recognition motifs unique to BacA/UppP enzymes. The verification of our proposed active-site residues would provide new strategies for the development of substratespecific inhibitors which mimic both the lipid and pyrophosphate moieties, leading to the development of novel antimicrobial agents.

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Section: Biosynthesis Of the Eukaryotic Dolichyl Lipid Carriersmentioning

confidence: 99%

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Bickford

Nick

2013

Microbiology

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“…[3][4][5][6] We combined this technology with SNP-homozygosity mapping and targeted sequence capture to identify likely causative genes in a syndrome of neonatal-onset inflammatory skin and bowel disease in two siblings.…”

Section: Sum M a R Ymentioning

confidence: 99%

“…1,2 High-throughput sequence technology can be used to identify rare but penetrant disease-associated mutations in affected members of families with mendelian conditions. [3][4][5][6] We combined this technology with SNP-homozygosity mapping and targeted sequence capture to identify likely causative genes in a syndrome of neonatal-onset inflammatory skin and bowel disease in two siblings.…”

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confidence: 99%

Inflammatory Skin and Bowel Disease Linked toADAM17Deletion

et al. 2011

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SUM M A R YWe performed genetic and immunohistochemical studies in a sister and brother with autosomal recessive neonatal inflammatory skin and bowel lesions. The girl died suddenly at 12 years of age from parvovirus B19-associated myocarditis; her brother had mild cardiomyopathy. We identified a loss-of-function mutation in ADAM17, which encodes a disintegrin and metalloproteinase 17 (also called tumor necrosis factor α [TNF-α]-converting enzyme, or TACE), as the probable cause of this syndrome. Peripheral-blood mononuclear cells (PBMCs) obtained from the brother at 17 years of age showed high levels of lipopolysaccharide-induced production of interleukin-1β and interleukin-6 but impaired release of TNF-α. Despite repeated skin infections, this young man has led a relatively normal life. (Funded by Barts and the London Charity and the European Commission Seventh Framework Programme.) I nflammatory disorders of the skin and gut, including eczema, psoriasis, and celiac disease, have been linked to changes in barrier function and immune responses, by means of genetic and functional studies. Large casecontrol studies combined with genomewide association studies have identified common genetic risk factors, with low penetrance, for a plethora of human disorders. Such studies have also identified numerous single-nucleotide polymorphisms (SNPs) in genes linked to the regulation of immunity and inflammation affecting epithelial tissues. 1,2High-throughput sequence technology can be used to identify rare but penetrant disease-associated mutations in affected members of families with mendelian conditions. [3][4][5][6] We combined this technology with SNP-homozygosity mapping and targeted sequence capture to identify likely causative genes in a syndrome of neonatal-onset inflammatory skin and bowel disease in two siblings. C A SE R EP OR TTwo of three children born to consanguineous parents (first cousins) of Lebanese origin had the same clinical features involving the skin, hair, and gut. The skin lesions developed on the second day of life, with diarrhea developing in the first week of life. The affected girl died at 12 years of age from fulminant parvovirus B19-associatedThe New England Journal of Medicine Downloaded from nejm.org at MAX DELBRUECK CENTRUM FOR MOLECULAR MED on April 2, 2014. For personal use only. No other uses without permission.

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“…Infantile cataract might occur in various inborn errors of metabolism including galactosemia, peroxisomal disorders, and mitochondrial disorders. Cataract has been described in PMM2-CDG adult patients, but in children it is a rare clinical finding only described in a few ALG 8-CDG (CDG-Ih), ALG2-CDG (CDG-Ii), and in CDG-Ix patients (Thiel et al 2003;Eklund et al 2005;Morava et al 2008); nevertheless, cataract is an important symptom in SRD5A3-CDG (Cantagrel et al 2010 andKahrizi et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?

et al. 2011

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Congenital disorders of glycosylation (CDG) are genetic diseases caused by abnormal protein and lipid glycosylation. In this chapter, we report the clinical, biochemical, and molecular findings in two siblings with an unidentified CDG (CDG-Ix). They are the first and the third child of healthy consanguineous Argentinean parents. Patient 1 is now a 11-year-old girl, and patient 2 died at the age of 4 months. Their clinical picture involved liver dysfunction in the neonatal period, psychomotor retardation, microcephaly, seizures, axial hypotonia, feeding difficulties, and hepatomegaly. Patient 1 also developed strabismus and cataract. They showed a type 1 pattern of serum sialotransferrin. Enzymatic analysis for phosphomannomutase and phosphomannose isomerase in leukocytes and fibroblasts excluded PMM2-CDG and MPI-CDG. Lipid-linked oligosaccharide (LLO) analysis showed a normal profile. Therefore, this result could point to a deficiency in the dolichol metabolism. In this context, ALG8-CDG, DPAGT1-CDG, and SRD5A3-CDG were analyzed and no defects were identified. In conclusion, we could not identify the genetic deficiency in these patients yet. Further studies are underway to identify the basic defect in them, taking into account the new CDG types that have been recently described.

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Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3

Cited by 56 publications

References 7 publications

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Inflammatory Skin and Bowel Disease Linked toADAM17Deletion

Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?

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