scholarly journals Novel compound heterozygous frameshift variants in WDR81 associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms WDR81 involvement

2021 ◽  
Author(s):  
Jiasun Su ◽  
Weiliang Lu ◽  
Mengting Li ◽  
Qiang Zhang ◽  
Fei Chen ◽  
...  
Keyword(s):  
Congenital Hydrocephalus ◽  
Compound Heterozygous ◽  
Brain Anomalies

scholarly journals Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Florent Marguet ◽  
Myriam Vezain ◽  
Pascale Marcorelles ◽  
Séverine Audebert-Bellanger ◽  
Kévin Cassinari ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Wnt Signaling Pathway ◽  
Brain Lesions ◽  
Congenital Hydrocephalus ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Defects Classification

AbstractThe prevalence of congenital hydrocephalus has been estimated at 1.1 per 1000 infants when including cases diagnosed before 1 year of age after exclusion of neural tube defects. Classification criteria are based either on CSF dynamics, pathophysiological mechanisms or associated lesions. Whereas inherited syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus either isolated or as a major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. In the past 10 years, pathogenic variants in CCDC88C have been documented but the neuropathology remains virtually unknown. We report the neuropathology of two foetuses from one family harbouring two novel compound heterozygous pathogenic variants in the CCDC88C gene: a maternally inherited indel in exon 22, c.3807_3809delinsACCT;p.(Gly1270Profs*53) and a paternally inherited deletion of exon 23, c.3967-?_c.4112-?;p.(Leu1323Argfs*10). Medical termination of pregnancy was performed at 18 and 23 weeks of gestation for severe bilateral ventriculomegaly. In both fetuses, brain lesions consisted of multifocal atresia-forking along the aqueduct of Sylvius and the central canal of the medulla, periventricular neuronal heterotopias and choroid plexus hydrops. The second fetus also presented lumbar myelomeningocele, left diaphragmatic hernia and bilateral renal agenesis. CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3. Interestingly, heterozygous variants in PARD3 result in neural tube defects by defective tight junction formation and polarization process of the neuroepithelium. Besides, during organ formation Wnt signalling is a prerequisite for planar cell polarity pathway activation, and mutations in planar cell polarity genes lead to heart, lung and kidney malformations. Hence, candidate variants in CCDC88C should be carefully considered whether brain lesions are isolated or associated with malformations suspected to result from disorders of planar cell polarity.

Severe cystic fibrosis associated with a DeltaF508/R347H+D979A compound heterozygous genotype

1998 ◽  
Vol 53 (1) ◽  
pp. 50-53 ◽  
Author(s):  
Satoko Hojo ◽  
Jiro Fujita ◽  
Hiroshi Miyawaki ◽  
Yuka Obayashi ◽  
Jiro Takahara ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Compound Heterozygous ◽  
Heterozygous Genotype

Ultrasound Diagnosis of Congenital Brain Anomalies: about 46 cases

2016 ◽  
Vol 76 (05) ◽  
Author(s):  
A Morchdi ◽  
F Rebhi ◽  
A Gharsa ◽  
C Abid ◽  
D Chelli
Keyword(s):  
Ultrasound Diagnosis ◽  
Brain Anomalies ◽  
Congenital Brain Anomalies

Isolated Familial Plasminogen Deficiency May not Be a Risk Factor for Thrombosis

1996 ◽  
Vol 76 (06) ◽  
pp. 1004-1008 ◽  
Author(s):  
R C Tait ◽  
Isobel D Walker ◽  
J A Conkie ◽  
S I A M Islam ◽  
Frances McCall
Keyword(s):  
Risk Factor ◽  
Prevalence Rate ◽  
Blood Donors ◽  
Compound Heterozygous ◽  
Thrombotic Risk ◽  
Deficiency State ◽  
Thrombotic Risk Factor ◽  
Plasminogen Deficiency ◽  
Old Donor ◽  
Heterozygous Deficiency

SummaryDespite many reports of individuals with congenital plasminogen deficiency and thrombosis, there is still uncertainty whether heterozygous deficiency represents a real thrombophilic risk factor or simply a coincidental finding. We have addressed this issue by testing for plasminogen deficiency in a cohort of 9611 blood donors. Out of 66 donors with reduced plasminogen activity on two occasions 28 were shown to have a familial deficiency state (including 3 with dysplasminogen-aemia). Our observed prevalence rate for familial plasminogen deficiency, calculated at 2.9/1000 (95% Cl = 1.9-4.2 per 1000), was not significantly different from that calculated from published reports of congenital plasminogen deficiency in thrombotic cohorts (5.4/1000). Furthermore, with only two exceptions, all 80 donors and relatives with familial deficiency were asymptomatic with regard to thrombosis -including a 29 year old donor with suspected compound heterozygous hypoplasminogenaemia. These findings add further weight to the argument that familial heterozygous plasminogen deficiency, at least in isolation, does not constitute a significant thrombotic risk factor. However, it remains uncertain whether plasminogen deficiency, when combined with other thrombophilic conditions, may become more clinically important.

Prenatal Diagnosis of Compound Heterozygous Deficiency of Protein C by Direct Detection of the Mutation Sites

1996 ◽  
Vol 76 (02) ◽  
pp. 277-278 ◽  
Author(s):  
Masaru Ido ◽  
Tatsuya Hayashi ◽  
Junji Nishioka ◽  
Masazumi Itoh ◽  
Hiroyuki Minoura ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Protein C ◽  
Direct Detection ◽  
Compound Heterozygous ◽  
Heterozygous Deficiency

Reconsidering NMIHBA Core Features: Macrocephaly Is Not a So Unusual Sign in PRUNE1-Related Encephalopathy

2020 ◽  
Author(s):  
Roberta Battini ◽  
Enrico Bertini ◽  
Roberta Milone ◽  
Chiara Aiello ◽  
Rosa Pasquariello ◽  
...  
Keyword(s):  
Nervous System ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Neurodevelopmental Disorder ◽  
Recurrent Mutation ◽  
Clinical Suspicion ◽  
Alexander Disease ◽  
Brain Anomalies ◽  
Progressive Encephalopathy ◽  
Core Features

Abstract PRUNE1-related disorders manifest as severe neurodevelopmental conditions associated with neurodegeneration, implying a differential diagnosis at birth with static encephalopathies, and later with those manifesting progressive brain damage with the involvement of both the central and the peripheral nervous system.Here we report on another patient with PRUNE1 (p.Asp106Asn) recurrent mutation, whose leukodystrophy, inferior olives hyperintensity, and macrocephaly led to the misleading clinical suspicion of Alexander disease. Clinical features, together with other recent descriptions, suggest avoiding the term “microcephaly” in defining this disorder that could be renamed “neurodevelopmental disorder with progressive encephalopathy, hypotonia, and variable brain anomalies” (NPEHBA).

Anti-Myelin Oligodendrocyte Glycoprotein Encephalomyelitis and Extensive Longitudinal Transverse Myelitis Associated with Compound Heterozygous NLRP3 Missense Mutations in a Young Child

2020 ◽  
Author(s):  
Deirdre O'Sullivan ◽  
Michael Moore ◽  
Susan Byrne ◽  
Andreas O. Reiff ◽  
Susanna Felsenstein
Keyword(s):  
Young Child ◽  
Genetic Basis ◽  
Transverse Myelitis ◽  
Acute Disseminated Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Childhood Onset

AbstractAcute disseminated encephalomyelitis in association with extensive longitudinal transverse myelitis is reported in a young child with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody with heterozygous NLRP3 missense mutations; p.(Arg488Lys) and p.(Ser159Ile). This case may well present an exceptional coincidence, but may describe a yet unrecognized feature of the spectrum of childhood onset cryopyrinopathies that contribute to the understanding of the genetic basis for anti-MOG antibody positive encephalomyelitis. Based on this observation, a larger scale study investigating the role of NLRP3 and other inflammasomes in this entity would provide important pathophysiological insights and potentially novel avenues for treatment.

DEVELOPMENTAL BRAIN ANOMALIES ASSOCIATED WITH INTRAUTERINE HYDROCEPHALUS

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
P Humphreys ◽  
D Muzumdar ◽  
L Sly ◽  
E Ventureyra ◽  
M Vassilyadi
Keyword(s):  
Brain Anomalies
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