scholarly journals Posterior Lissencephaly Associated with Subcortical Band Heterotopia Due to a Variation in the CEP85L Gene: A Case Report and Refining of the Phenotypic Spectrum

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1208
Author(s):  
Gianluca Contrò ◽  
Alessia Micalizzi ◽  
Sara Giangiobbe ◽  
Stefano Giuseppe Caraffi ◽  
Roberta Zuntini ◽  
...  
Keyword(s):  
Case Report ◽  
De Novo ◽  
Brain Mri ◽  
Psychomotor Development ◽  
Present Case Report ◽  
Whole Exome ◽  
Subcortical Band Heterotopia ◽  
Double Cortex ◽  
Cerebral Convolutions

Lissencephaly describes a group of conditions characterized by the absence of normal cerebral convolutions and abnormalities of cortical development. To date, at least 20 genes have been identified as involved in the pathogenesis of this condition. Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. Here, we describe a 3-year-old boy with slightly delayed psychomotor development and mild dysmorphic features, including bitemporal narrowing, protruding ears with up-lifted lobes and posterior plagiocephaly. Brain MRI at birth identified type 1 lissencephaly, prevalently in the temporo–occipito–parietal regions of both hemispheres with “double-cortex” (Dobyns’ 1–2 degree) periventricular band alterations. Whole-exome sequencing revealed a previously unreported de novo pathogenic variant in the CEP85L gene (NM_001042475.3:c.232+1del). Only 20 patients have been reported as carriers of pathogenic CEP85L variants to date. They show lissencephaly with prevalent posterior involvement, variable cognitive deficits and epilepsy. The present case report indicates the clinical variability associated with CEP85L variants that are not invariantly associated with severe phenotypes and poor outcome, and underscores the importance of including this gene in diagnostic panels for lissencephaly.

scholarly journals Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes

2020 ◽  
Author(s):  
Aldesia Provenzano ◽  
Andrea La Barbera ◽  
Mirko Scagnet ◽  
Angelica Pagliazzi ◽  
Giovanna Traficante ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Chromatin Remodeling ◽  
Brain Mri ◽  
Cranial Bone ◽  
Genetic Syndromes ◽  
Whole Exome ◽  
Cerebellar Tonsillar Herniation ◽  
Brain Magnetic Resonance Image

AbstractType 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3–5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees.

scholarly journals Case report : a novel ASXL3 gene variant in a Sudanese boy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke Wu ◽  
Yan Cong
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Psychomotor Development ◽  
Gene Variant ◽  
Feeding Difficulties ◽  
Severe Intellectual Disability ◽  
Whole Exome

Abstract Background Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, moderate to severe intellectual disability, poor or absent speech, feeding difficulties, growth failure, dysmorphic craniofacial features and minor skeletal features. The aim of this study was to investigate the genetic etiology of a Sudanese boy with severe developmental delay, intellectual disability, and craniofacial phenotype using trio-based whole-exome sequencing. To our knowledge, no patients with ASXL3 gene variant c.3043C>T have been reported detailedly in literature. Case presentation The patient (male, 3 years 6 months) was the first born of a healthy non-consanguineous couple originating from Sudan, treated for “psychomotor retardation” for more than 8 months in Yiwu. The patient exhibited severely delayed milestones in physiological and intellectual developmental stages, language impairment, poor eye-contact, lack of subtle motions of fingers, fear of claustrophobic space, hypotonia, clinodactyly, autistic features. Peripheral blood samples were collected from the patient and his parents. Trio-based whole-exome sequencing(Trio-WES) identified a de novo heterozygous ASXL3 gene variant c.3043C>T;p.Q1015X. Sanger sequencing verified variants of this family. Conclusion Trio-WES analysis identified a de novo nonsense variant (c.3043C>T) of ASXL3 gene in a Sudanese boy. To our knowledge, the patient with this variant has not been reported previously in literature. This study presents a new case for ASXL3 gene variants, which expanded the mutational and phenotypic spectrum.

scholarly journals Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

2019 ◽  
Author(s):  
Sofia Thunström ◽  
Markus Axelsson
Keyword(s):  
Case Report ◽  
Peripheral Neuropathy ◽  
De Novo ◽  
Age Of Onset ◽  
De Novo Mutation ◽  
Missense Mutations ◽  
Dural Ectasia ◽  
Whole Exome ◽  
Demyelinating Peripheral Neuropathy ◽  
Multiple Cysts

Abstract Background: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. Case Presentation: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686T>G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. Conclusions: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes. Keywords: Leukoencephalopathia, demyelinating peripheral neuropathy, dural ectasia explained, de novo mutation, the SAMD9L gene.

scholarly journals Clinical Case of Pregnancy and Follow-Up of Bartter Syndrome (Type II) with a Novel Mutation

2020 ◽  
pp. 1-5
Author(s):  
Laura Lūse ◽  
Anna Miskova ◽  
Dace Rezeberga ◽  
Gita Jansone ◽  
Kristīne Rasnača ◽  
...  
Keyword(s):  
Case Report ◽  
Clinical Case ◽  
Clinical Course ◽  
Novel Mutation ◽  
Bartter Syndrome ◽  
Psychomotor Development ◽  
Syndrome Type ◽  
Type Ii ◽  
Present Case Report ◽  
Normal Ranges

Background: Bartter syndrome is a rare autosomal recessive inherited salt wasting tubulopathy, it`s incidence proportion is 1.2 cases per 1.000.000 live births. The present case - report discusses a clinical case of an antenatal Bartter syndrome (type II) with a novel mutation and it`s course from antenatal presentation to 6 months postpartum. Case Presentation: The case-report discusses a clinical case of an antenatal Bartter syndrome (type II) with a novel homozygous missense variant mutation in KCNJ1 gene: c.554C>T (p. Pro185Leu). Symptoms presented from 24 weeks of pregnancy as premature labour threats, maternal dyspnoea and severe polyhydramnios (amniotic fluid index 36 cm). Therapeutic interventions included use of indomethacin, dexamethasone, micronized progesterone and three consequent amnioreductions. Pregnancy was prolonged until 32 weeks and induced due to severe reoccurring polyhydramnios, progressing maternal dyspnoea and inability to perform next amnioreduction. Labour was complicated by severe placental abruption and new born – boy was referred to neonatal intensive care unit. Neonatal period was complicated by electrolyte abnormalities: hyponatremia, hypochloremic metabolic alkalosis, transient hyperkalaemia that gradually developed into hypokalaemia, hypercalcemia and elevated rennin and aldosterone levels characteristic to type II Bartter syndrome. At 6 months (corrected age 4 months) he is gaining weight within normal ranges and his psychomotor development is ahead of his corrected age, without any need for daily medications. Conclusion: The present case report describes the clinical course of a Bartter syndrome is of high importance, due to the reason that it shows clinical course of patient with novel mutation and offers one of the ways how to manage the disease. The described novel mutation may have favourable prognosis for neonate. The pregnancy should be managed as high-risk pregnancy with expertise in perinatal diagnostics and interventions. Early recognition, and interventions, are and essential to prolong a pregnancy and lessen prematurity complications.

scholarly journals Case Report: A Novel PAX3 Mutation Associated With Waardenburg Syndrome Type 1

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiuming Hu ◽  
Huazhong Ma ◽  
Jiawei Shen ◽  
Zongming Zhuang ◽  
Jianqiang Li ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Test ◽  
Novel Mutation ◽  
Present Report ◽  
Hereditary Disease ◽  
Chinese Family ◽  
Syndrome Type ◽  
Waardenburg Syndrome ◽  
Whole Exome

Background: Waardenburg Syndrome Type 1 (WS1) is a rare hereditary disease, which is usually caused by the mutations of PAX3 (paired box 3). Here, we reported a pedigree with WS1, which was caused by a novel mutation in PAX3.Case Report: In this present report, a 10-year-old boy and his twin sister from a Han Chinese family presented with iris pigmentary abnormality, synophrys, and broad and high nasal root. Their father presented premature whitening of the hair, but no iris pigmentary abnormality. Their aunts presented the same clinical characteristics with the twins and premature graying of hair. However, none of the patients reported hearing loss. The clinical diagnosis of the four patients from this pedigree was WS1. The whole exome sequencing (WES) revealed a novel mutation (c.959-5T>G) in the PAX3 gene, which could be responsible for the observed pathogenic of WS1 in this pedigree. The genetic test confirmed the diagnosis of WS1 in the four patients from the studied pedigree.Conclusion: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS1. The newly identified PAX3 gene mutation can expand the understanding of WS1.

Unusual Chromosomal Rearrangement Resulted in Interstitial Monosomy 9p: Case Report

2016 ◽  
Vol 148 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ceren D. Durmaz ◽  
Kanay Yararbaş ◽  
Nüket Y. Kutlay ◽  
Özlem Türedi ◽  
İsmigül Akın ◽  
...  
Keyword(s):  
Case Report ◽  
Congenital Malformations ◽  
Chromosomal Rearrangement ◽  
De Novo ◽  
Psychomotor Development ◽  
Molecular Karyotyping ◽  
Fish Analysis ◽  
Chromosome 13 ◽  
Craniofacial Dysmorphism ◽  
Cytogenetic Studies

We report on a 4.5-year-old boy with interstitial monosomy 9p in a unique and complex de novo rearrangement. The patient had been referred for craniofacial dysmorphism, delayed psychomotor development, and various congenital malformations. We combined cytogenetic studies and FISH analyses to delineate the deletion. The result of our cytogenetic studies was 46,XY,der(9)(p22pter). In order to confirm the deletion, we also performed FISH analysis, which showed that the 9p subtelomeric region was inserted into chromosome 13. Molecular karyotyping was performed to describe the exact genomic breakpoints of the rearrangement. In conclusion, this case is a complex insertion/deletion abnormality which has not been reported before.

scholarly journals When Familial Hearing Loss Means Genetic Heterogeneity: A Model Case Report

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1636
Author(s):  
Camille Cenni ◽  
Luke Mansard ◽  
Catherine Blanchet ◽  
David Baux ◽  
Christel Vaché ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Case Report ◽  
De Novo ◽  
Panel Analysis ◽  
Adult Onset ◽  
Childhood Onset ◽  
Model Case ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Neonatal Thrombocytopenia

We describe a family with both hearing loss (HL) and thrombocytopenia, caused by pathogenic variants in three genes. The proband was a child with neonatal thrombocytopenia, childhood-onset HL, hyper-laxity and severe myopia. The child’s mother (and some of her relatives) presented with moderate thrombocytopenia and adulthood-onset HL. The child’s father (and some of his relatives) presented with adult-onset HL. An HL panel analysis, completed by whole exome sequencing, was performed in this complex family. We identified three pathogenic variants in three different genes: MYH9, MYO7A and ACTG1. The thrombocytopenia in the child and her mother is explained by the MYH9 variant. The post-lingual HL in the paternal branch is explained by the MYO7A variant, absent in the proband, while the congenital HL of the child is explained by a de novo ACTG1 variant. This family, in which HL segregates, illustrates that multiple genetic conditions coexist in individuals and make patient care more complex than expected.

scholarly journals Spinocerebellar Ataxia type 29 in a family of Māori descent

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Kathie J. Ngo ◽  
Gemma Poke ◽  
Katherine Neas ◽  
Brent L. Fogel
Keyword(s):  
Spinocerebellar Ataxia ◽  
Autosomal Dominant ◽  
De Novo ◽  
Spinocerebellar Ataxia Type ◽  
Case Presentation ◽  
Whole Exome ◽  
Progressive Cerebellar Ataxia ◽  
Genetic Origins ◽  
Trisphosphate Receptor

Abstract Background Mutations in the Inositol 1,4,5-Trisphosphate Receptor Type 1 (ITPR1) gene cause spinocerebellar ataxia type 29 (SCA29), a rare congenital-onset autosomal dominant non-progressive cerebellar ataxia. The Māori, indigenous to New Zealand, are an understudied population for genetic ataxias. Case presentation We investigated the genetic origins of spinocerebellar ataxia in a family of Māori descent consisting of two affected sisters and their unaffected parents. Whole exome sequencing identified a pathogenic variant, p.Thr267Met, in ITPR1 in both sisters, establishing their diagnosis as SCA29. Conclusions We report the identification of a family of Māori descent with a mutation causing SCA29, extending the worldwide scope of this disease. Although this mutation has occurred de novo in other populations, suggesting a mutational hotspot, the children in this family inherited it from their unaffected mother who was germline mosaic.

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