Pathogenic Compound-Heterozygous PARN Variant Mimicking Pontocerebellar Hypoplasia Type 2A

2021 ◽  
Author(s):  
Anna-Lena Klauser ◽  
Miriam Erlacher ◽  
Wibke G. Janzarik
Keyword(s):  
Compound Heterozygous ◽  
Pontocerebellar Hypoplasia

scholarly journals Clinical and genetic characteristics of ponto-cerebellar hypoplasia caused by mutations in the TSEN54 gene (OMIM: 277470)

2019 ◽  
Vol 9 (2) ◽  
pp. 30-36
Author(s):  
E. I. Dadali ◽  
I. A. Akimova ◽  
N. A. Semenova ◽  
D. M. Guseva ◽  
O. A. Shchagina ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Compound Heterozygous ◽  
Pontocerebellar Hypoplasia ◽  
Genetic Characteristics ◽  
Molecular Genetic Diagnosis ◽  
Severity Of The Disease ◽  
Detection Of Mutations ◽  
Compound Heterozygous State

Introduction. The description of the clinical and genetic characteristics of eight patients with autosomal-recessive variant pontocerebellar hypoplasia due to mutations in the TSEN54 gene.Purpose. Description of clinical and genetic characteristics of Russian patients with type 2A and type 4 of pontocerebellar hypoplasia.Materials and methods. The diagnosis of pontocerebellar hypoplasia was established on the basis of the specific features of clinical manifestations and detection of mutations in the gene TSEN54 based on the analysis of the results of exome sequencing. Results. 8 patients with pontocerebellar hypoplasia caused by mutations in the TSEN54 gene were identified. Discussion. Based on the features of clinical manifestations and severity of the disease in 5 patients diagnosed pontocerebellar hypoplasia type 2A, and in 3 patients – type 4. In patients with type 2A of pontocerebellar hypoplasia discovered mutation c. 919G>T (p.Ala307Ser)  in a homozygous state. Patients with type 4 of pontocerebellar hypoplasia this mutation is detected in the compound heterozygous state with c.670_671delAA (p.Lys224fs) and c.1264C>T (p.Gln422fs).Conclusion. The obtained results allow us to conclude that, as well as in European populations, the mutation c.919G>T (p. Ala307Ser) is a major in Russian patients with pontocerebellar hypoplasia 2A and 4 types, which account for about half of all cases of this disease group. The search for this mutation should be the first stage of molecular genetic diagnosis in patients with clinical and magnetic resonance signs of pontocerebellar hypoplasia.

scholarly journals Diagnosis of SLC25A46-related pontocerebellar hypoplasia in two siblings with fulminant neonatal course: role of postmortem CT and whole genomic analysis: a case report

BMC Neurology ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Mamiko Yamada ◽  
Hisato Suzuki ◽  
Hiroyuki Adachi ◽  
Atsuko Noguchi ◽  
Fuyuki Miya ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Postmortem Brain ◽  
Compound Heterozygous ◽  
Whole Genome ◽  
Pontocerebellar Hypoplasia ◽  
Whole Genome Analysis ◽  
Neonatal Deaths ◽  
Radiologic Findings ◽  
Long Read ◽  
Compound Heterozygous Variants

Abstract Background Pontocerebellar hypoplasia (PCH) is increasingly known as a degenerative disease rather than simple “hypoplasia”. At least 21 disease-causing genes have been identified for PCH so far. Because PCH is very heterogenous, prognostic prediction based solely on clinical or radiologic findings is not feasible. Case presentation Here, we report two siblings who had a fulminant neonatal course. The documentation of pontocerebellar hypoplasia by postmortem brain CT imaging in one of the siblings and a subsequent complex and comprehensive whole genome analysis established that both siblings had bi-allelic compound heterozygous variants (a splicing variant and a deletion) in the SLC25A46 gene which encodes a solute carrier protein essential for mitochondrial function. Long-read whole genome sequencing was required to confirm the presence of the deletion. The fulminant courses suggest that SLC25A46-related PCH is an acutely progressive degenerative condition starting in utero, rather than a simple static hypoplasia. Conclusion The genomic analysis was instrumental and essential to solving the enigma of the unexplained neonatal deaths of these two siblings and to provide accurate genetic counseling.

Two siblings with a novel variant of EXOSC3 extended phenotypic spectrum of pontocerebellar hypoplasia 1B to an exceptionally mild form

2021 ◽  
Vol 14 (1) ◽  
pp. e236732
Author(s):  
Weiyi Mu ◽  
Teresa Heller ◽  
Kristin W Barañano
Keyword(s):  
Autosomal Recessive ◽  
Phenotypic Variability ◽  
Compound Heterozygous ◽  
Pontocerebellar Hypoplasia ◽  
Neurocognitive Impairments ◽  
Pathogenic Variants ◽  
Novel Variant ◽  
A Subunit ◽  
Rna Exosome ◽  
Exosome Complex

Pontocerebellar hypoplasia type 1B (PCH1B) describes an autosomal recessive neurological condition that involves hypoplasia or atrophy of the cerebellum and pons, resulting in neurocognitive impairments. Although there is phenotypic variability, this is often an infantile lethal condition, and most cases have been described to be congenital and neurodegenerative. PCH1B is caused by mutations in the gene EXOSC3, which encodes exosome component 3, a subunit of the human RNA exosome complex. A range of pathogenic variants with some correlation to phenotype have been reported. The most commonly reported pathogenic variant in EXOSC3 is c.395A>C, p.(Asp132Ala); homozygosity for this variant has been proposed to lead to milder phenotypes than compound heterozygosity. In this case, we report two siblings with extraordinarily mild presentations of PCH1B who are compound heterozygous for variants in EXOSC3 c.155delC and c.80T>G. These patients drastically expand the phenotypic variability of PCH1B and raise questions about genotype–phenotype associations.

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

Natural course of pontocerebellar hypoplasia Type 2

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
I Sánchez Albisua ◽  
S Froelich ◽  
I Krägeloh-Mann
Keyword(s):  
Natural Course ◽  
Pontocerebellar Hypoplasia

Pontocerebellar Hypoplasia Type 9: A New Subtype

2015 ◽  
Vol 46 (S 01) ◽  
Author(s):  
A. Lustenberger ◽  
J. Lemke ◽  
G. Borck ◽  
S. Grunt ◽  
M. Steinlin
Keyword(s):  
Pontocerebellar Hypoplasia

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

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.

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