Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation

Morava, Éva; Lefeber, Dirk; Urban, Zsolt; Meırleır, Linda De; Meinecke, Peter; Kaesbach, G. Gillessen; Sykut-Cegielska, Jolanta; Adamowicz, Maciej; Salafsky, Ira S.; Ranells, Judith D.; Lemyre, Emmanuelle; Reeuwijk, Jeroen van; Brunner, Han G.; Wevers, Ron A.

doi:10.1038/sj.ejhg.5201947

Cited by 67 publications

(71 citation statements)

References 20 publications

(20 reference statements)

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“…The increased occurrence of oligomannosidic glycans has been explained by mislocalization of the 1,2-Nacetylglucosaminyltransferase 1 and mannosidase II enzymes in the medial Golgi (32 ). Mutations in the a2 subunit of the vacuolar H ϩ -ATPase (ATP6V0A2) (33,34 ) cause impaired Golgi trafficking via altering the intracellular pH gradient and produce glycosylation abnormalities at several levels. Unlike MGAT2 and B4GALT1 mutations, Golgi-trafficking defects affect multiple steps in the N-glycan processing pathway, as can be observed by the wide range of truncated glycan structures.…”

Section: Discussionmentioning

confidence: 99%

Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II

et al. 2011

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BACKGROUND:Determination of the genetic defect in patients with a congenital disorder of glycosylation (CDG) is challenging because of the wide clinical presentation, the large number of gene products involved, and the occurrence of secondary causes of underglycosylation. Transferrin isoelectric focusing has been the method of choice for CDG screening; however, improved methods are required for the molecular diagnosis of patients with CDG type II.

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Section: Discussionmentioning

confidence: 99%

Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II

et al. 2011

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“…Patients have suggestive facial features with hanging eyelids, down-slanting palpebral fissures, muscle hypotonia, epilepsy and mild-to-moderate developmental delay. 2,12,14 The combination of the biochemical marker of abnormal protein glycosylation (congenital disorder of glycosylation (CDGII)) and cobblestone-like brain dysgenesis in ARCL2 is pathognomonic for ARCL2A. 2,15,16 The recently defined ARCL2B is caused by mutations in the PYCR1 gene, involved in de novo mitochondrial proline synthesis, leading to a progeroid appearance, parchment-like skin, triangular face, joint luxations, muscle hypotonia, dystonic posturing and developmental delay.…”

Section: Introductionmentioning

confidence: 99%

Clinical and biochemical features guiding the diagnostics in neurometabolic cutis laxa

et al. 2013

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Patients with cutis laxa (CL) have wrinkled, sagging skin with decreased elasticity. Skin symptoms are associated with variable systemic involvement. The most common, genetically highly heterogeneous form of autosomal recessive CL, ARCL2, is frequently associated with variable metabolic and neurological symptoms. Progeroid symptoms, dysmorphic features, hypotonia and psychomotor retardation are highly overlapping in the early phase of these disorders. This makes the genetic diagnosis often challenging. In search for discriminatory symptoms, we prospectively evaluated clinical, neurologic, metabolic and genetic features in our patient cohort referred for suspected ARCL. From a cohort of 26 children, we confirmed mutations in genes associated with ARCL in 16 children (14 probands), including 12 novel mutations. Abnormal glycosylation and gyration abnormalities were mostly, but not always associated with ATP6V0A2 mutations. Epilepsy was most common in ATP6V0A2 defects. Corpus callosum dysgenesis was associated with PYCR1 and ALDH18A1 mutations. Dystonic posturing was discriminatory for PYCR1 and ALDH18A1 defects. Metabolic markers of mitochondrial dysfunction were found in one patient with PYCR1 mutations. So far unreported white matter abnormalities were found associated with GORAB and RIN2 mutations. We describe a large cohort of CL patients with neurologic involvement. Migration defects and corpus callosum hypoplasia were not always diagnostic for a specific genetic defect in CL. All patients with ATP6V0A2 defects had abnormal glycosylation. To conclude, central nervous system and metabolic abnormalities were discriminatory in this genetically heterogeneous group, although not always diagnostic for a certain genetic defect in CL.

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“…Autosomal recessive cutis laxa (ARCL) is associated with a progeroid appearance, lax and wrinkled skin, osteopenia, and mental retardation (Morava et al 2008). One of the major diagnostic criteria is abnormal elastin fibers ), but the genetic deficiencies of many cutis laxa patients were unknown.…”

Section: Vacuolar Atpasementioning

confidence: 99%

Golgi Glycosylation and Human Inherited Diseases

Freeze¹,

Ng²

2011

Cold Spring Harbor Perspectives in Biology

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Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation

Cited by 67 publications

References 20 publications

Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II

Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II

Clinical and biochemical features guiding the diagnostics in neurometabolic cutis laxa

Golgi Glycosylation and Human Inherited Diseases

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