DMP1-CDG (CDG1e) with Significant Gastrointestinal Manifestations; Phenotype and Genotype Expansion

Bursle, Carolyn; Brown, Dominique; Cardinal, John; Connor, Frances; Calvert, Sophie; Coman, David

doi:10.1007/8904_2016_7

Cited by 10 publications

(12 citation statements)

References 29 publications

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“…Diseaseassociated sequence variants of DPM1 cause congenital disorder of glycosylation type Ie (MIM #608799). To date, nine reported patients had typical features, including: seizure (8/9), postnatal microcephaly (8/9), abnormal MRI (8/9), and increased serum CK levels (7/9) [12]. Based on the detailed analysis of clinical findings, it is worth noting that the clinical features as well as paraclinical examinations of the reported proband are not consistent with the diagnosis of congenital disorder of glycosylation type Ie.…”

Section: Discussionmentioning

confidence: 96%

A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel–van der Aa syndrome

et al. 2018

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Helsmoortel-van der Aa (SWI/SNF autism-related or ADNP syndrome) is an autosomal dominant monogenic syndrome caused by de novo variants in the last exon of ADNP gene and no deletions have been documented to date. We report the first case of a 3 years and 10 months old boy exhibiting typical features of ADNP syndrome, including intellectual disability, autistic traits, facial dysmorphism, hyperlaxity, mood disorder, behavioral problems, and severe chronic constipation. 60K Agilent array-comparative genomic hybridization (CGH) identified a heterozygous interstitial microdeletion at 20q13.13 chromosome region, encompassing ADNP and DPM1. Taking into account the clinical phenotype of previously reported cases with ADNP single-point variants, genotype-phenotype correlation in the proband was established and the diagnosis of Helsmoortel-van der Aa syndrome was made. Our report thus confirms that ADNP haploinsufficiency is associated with Helsmoortel-van der Aa syndrome as well as highlights the utility of whole-genome array-CGH for detection of unbalanced submicroscopic chromosomal rearrangements in routine clinical setting in patients with unexplained intellectual disability and/or syndromic autism.

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Section: Discussionmentioning

confidence: 96%

A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel–van der Aa syndrome

et al. 2018

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“…Seizures were both focal (atonic, tonic, clonic, and myoclonic) as well as generalized (including absence). Non-neurological symptoms were more prominent in some patients, specifically gastrointestinal (with focal myoclonic and tonic seizures) ( 13 ). A detailed summary of symptoms in the above-mentioned articles can be found below in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review

et al. 2022

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Background: Mutations of genes involved in the synthesis of glycosylphosphatidylinositol and glycosylphosphatidylinositol-anchored proteins lead to rare syndromes called glycosylphosphatidylinositol-anchored proteins biosynthesis defects. Alterations of their structure and function in these disorders impair often fundamental processes in cells, resulting in severe clinical image. This study aimed to provide a systematic review of GPIBD cases reports published in English-language literature.Methods: The browsing of open-access databases (PubMed, PubMed Central. and Medline) was conducted, followed by statistical analysis of gathered information concerning neurological symptomatology. The inclusion criteria were: studies on humans, age at onset (<18 y.o.), and report of GPIBD cases with adequate data on the genetic background and symptomatology. Exclusion criteria were: publication type (manuscripts, personal communication, review articles); reports of cases of GPI biosynthesis genes mutations in terms of other disorders; reports of GPIBD cases concentrating on non-neurological symptoms; or articles concentrating solely on the genetic issues of GPI biosynthesis. Risk of bias was assessed using Joanna Brigs Institute Critical Appraisal Checklists. Data synthesis was conducted using STATISTICA 13.3.721.1 (StatSoft Polska Sp. z.o.o.). Used tests were chi-square, Fisher's exact test (for differences in phenotype), and Mann-Whitney U test (for differences in onset of developmental delay).Results: Browsing returned a total of 973 articles which, after ruling out the repetitions and assessing the inclusion and exclusion criteria, led to final inclusion of 77 articles (337 GPIBD cases) in the analysis. The main outcomes were prevalence of neurological symptoms, onset and semiology of seizures and their response to treatment, and onset of developmental delay. Based on this data a synthesis of phenotypical differences between the groups of GPIBD cases and the general GPIBD cases population was made.Discussion: A synthetical analysis of neurological components in clinical image of GPIBD patients was presented. It highlights the main features of these disorders, which might be useful in clinical practice for consideration in differential diagnosis with children presenting with early-onset seizures and developmental delay. The limitation of this review is the scarcity of the specific data in some reports, concerning the semiology and onset of two main features of GPIBD.

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“…The variant c.1A > C p.? has previously been reported to be linked to DPM1-CDG (CDG-Ie) ( Bursle et al, 2017 ). This variant is predicted to cause a loss of start codon and to interfere with initiation of translation.…”

Section: Resultsmentioning

confidence: 99%

“…To date, there are nine cases of DPM1-CDG reported in the literature ( Imbach et al, 2000 ; Kim et al, 2000 ; Garcia-Silva et al, 2004 ; Dancourt et al, 2006 ; Yan g et al, 2013 ; Bursle et al, 2017 ), comprising eight different variants in DPM1 ( Figure 3 ; Tables 1 , 2 ). One of the DPM1 variants we identified in the patient (c.1A > C p.?)…”

Section: Discussionmentioning

confidence: 99%

“…Deficiency of Dol-P-Man synthase, caused by variants in the DPM1 gene, is defined as DPM1-CDG and were first described in 2000 ( Imbach et al, 2000 ; Kim et al, 2000 ). Nine patients have been reported; they presented with intellectual disability, seizures, microcephaly, and dysmorphic features ( Imbach et al, 2000 ; Kim et al, 2000 ; Garcia-Silva et al, 2004 ; Dancourt et al, 2006 ; Yan g et al, 2013 ; Bursle et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: DPM1-CDG: Novel Variant with Severe Phenotype and Literature Review

et al. 2022

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Background: Congenital disorders of glycosylation (CDG) type I include variants in the DPM1 gene leading to DPM1-CDG. The nine previously reported patients showed developmental delay, seizures, electroencephalography abnormalities and dysmorphic features with varying disease onset and severity.Methods: Clinical features of a new patient are described. Whole exome sequencing using NGS was performed, followed by molecular simulation of the structural changes in the protein.Results: Our patient with DPM1-CDG presented with more severe symptoms and an earlier onset, specifically non-febrile seizures from the age of 3 weeks, global developmental delay, and severely retarded motor skills. She died at the age of 11 weeks after fulminant sepsis. We identified compound heterozygous variants in the DPM1 gene, one previously reported point mutation c.1A > C p.? as well as the novel variant c.239_241del p.(Lys80del), resulting in the first in-frame deletion located in exon 2. Loss of Lys80 may lead to an impaired α-helical configuration next to the GDP/GTP binding site.Conclusion: The presented case extends the spectrum of DPM1-CDG to a very young and severely affected child. The deletion of Lys80 in DPM1 results in an impaired helical configuration. This has implications for further understanding the association of structure and function of DPM1.

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DMP1-CDG (CDG1e) with Significant Gastrointestinal Manifestations; Phenotype and Genotype Expansion

Cited by 10 publications

References 29 publications

A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel–van der Aa syndrome

A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel–van der Aa syndrome

Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review

Case Report: DPM1-CDG: Novel Variant with Severe Phenotype and Literature Review

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