ISPD gene homozygous deletion identified by SNP array confirms prenatal manifestation of Walker–Warburg syndrome

Trkova, Marie; Krutilkova, Vera; Smetanová, D.; Bečvářová, Věra; Hlavova, E.; Jenčíková, N.; Hodačová, Jana; Hnykova, Lenka; Hroncova, Hana; Horáček, J; Stejskal, D.

doi:10.1016/j.ejmg.2015.05.004

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…The most severely affected patients present with profound brain malformation and ultimately do not survive infancy – a phenotype referred to as Walker–Warburg syndrome (Cormand et al, 2001). Affected individuals can display profound cognitive deficits, hydrocephaly (Box 2), and brain and retinal dysplasia, some of which may be observed by ultrasound during gestation (Vohra et al, 1993; Trkova et al, 2015). Other syndromes recognized in the spectrum of α-dystroglycanopathy include (in order of decreasing severity) muscle-eye-brain (MEB) disease, Fukuyama-type congenital muscular dystrophy, and several forms of congenital and limb-girdle muscular dystrophies (reviewed by Godfrey et al, 2011).…”

Section: Neurological Phenotypes In α-Dystroglycanopathiesmentioning

confidence: 99%

The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy

Nickolls

Bönnemann

2018

Disease Models &Amp; Mechanisms

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Dystroglycan is a cell membrane protein that binds to the extracellular matrix in a variety of mammalian tissues. The α-subunit of dystroglycan (αDG) is heavily glycosylated, including a special O-mannosyl glycoepitope, relying upon this unique glycosylation to bind its matrix ligands. A distinct group of muscular dystrophies results from specific hypoglycosylation of αDG, and they are frequently associated with central nervous system involvement, ranging from profound brain malformation to intellectual disability without evident morphological defects. There is an expanding literature addressing the function of αDG in the nervous system, with recent reports demonstrating important roles in brain development and in the maintenance of neuronal synapses. Much of these data are derived from an increasingly rich array of experimental animal models. This Review aims to synthesize the information from such diverse models, formulating an up-to-date understanding about the various functions of αDG in neurons and glia of the central and peripheral nervous systems. Where possible, we integrate these data with our knowledge of the human disorders to promote translation from basic mechanistic findings to clinical therapies that take the neural phenotypes into account.

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Section: Neurological Phenotypes In α-Dystroglycanopathiesmentioning

confidence: 99%

The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy

Nickolls

Bönnemann

2018

Disease Models &Amp; Mechanisms

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“…An earlier report of three prenatally diagnosed fetuses with WWS describes autopsy findings in the third fetus consisting of renal cysts and stenosis of the pyelo‐ureteral junction of the right kidney (Gasser et al, ). Recently, Gilbert‐Barness, Spicer, and Steffensen () reported unilateral kidney agenesis or cystic kidneys as possible association, and Trkova et al () described multicystic left kidney in a fetus with WWS and ISPD mutation.…”

Section: Introductionmentioning

confidence: 99%

Cystic kidneys in fetal Walker–Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature

Nabhan

Elkhateeb

Braun

et al. 2017

American J of Med Genetics Pt A

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Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy (CMD) secondary to α-dystroglycanopathy with muscle, brain and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least fifteen different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1) gene, the fukutin (FKTN) gene, the fukutin-related protein (FKRP) gene, the LARGE gene, the isoprenoid synthase domain-containing (ISPD) gene and other genes. We report on a family having four consecutive siblings affected by this condition with lethal outcome in three of them, and terminated pregnancy of the fourth based on antenatal fetal MRI complex brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising neurological involvement in the form of lissencephaly, subcortical/subependymal heterotopia and cerebellar hypoplasia shared by all four siblings, microphthalmia in one sibling, and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. By whole exome sequencing of the proband fetus, we identified a highly conserved missense mutation in the POMT2 gene that is known to cause congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, and Walker-Warburg syndrome. In conclusion, the heterogenous clinical presentation in the four affected siblings of this consanguineous family with POMT2 mutation expands the current clinical spectrum of POMT2 associated WWS to include large cystic kidneys; and further confirms intra-familial variability in terms of brain, kidney, and eye anomalies.

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“…WES reported ISPD gene mutations, c.674delC(p.A225Dfs*21) and c.1106T > G(p.V369G). it was consistent with Walker-Warburg syndrome (13). They nally decided to terminate the pregnancy.…”

Section: Wesmentioning

confidence: 82%

The Application of Late Amniocentesis: A Retrospective Study in a Tertiary Fetal Medicine Center in China

Yan

Chen

et al. 2020

Preprint

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Background: To assess the indications and complications of late amniocentesis, and the advantage of advanced genetic test results in a tertiary university fetal medical medicine unit.Methods: In this retrospective study, women that underwent amniocentesis at 24+0 to 39+4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy. Information was retrieved from patient medical records, checked by research staff, and analyzed. Results: Of the 1277 women (1311 fetuses) included, late detected sonographic abnormalities (86.2%) were the most common indication. The overall preterm birth and intrauterine demise rate were 2.6% and 1.2%, respectively, after amniocentesis. Sixty-six fetuses with aneuploidy (5.1%) and sixty-seven fetuses with pathogenic copy number variations (5.1%) were identified by chromosomal microarray analysis. One pathogenic copy number variation was detected by whole-exome sequencing. The maximal diagnostic yield (36.1%) was in the subgroup of fetuses with the abnormal noninvasive prenatal test, following by multiple abnormalities (23.8%). And 35.8% of the pregnancies were finally terminated.Conclusions: Due to the high detection rates of advanced genetic technologies and safety of the invasive procedure, it is reasonable to recommend late amniocentesis as an effective and credible method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Therefore, comprehensive genetic counseling is necessary.

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ISPD gene homozygous deletion identified by SNP array confirms prenatal manifestation of Walker–Warburg syndrome

Cited by 13 publications

References 14 publications

The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy

The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy

Cystic kidneys in fetal Walker–Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature

The Application of Late Amniocentesis: A Retrospective Study in a Tertiary Fetal Medicine Center in China

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