Clinical Features of de novo Pure 16q21q24.1 Chromosome Duplication

Pure partial duplications of the long arm of chromosome 16 are rare and few cases are described with delineation by chromosomal microarray. Data about clinical abnormalities of pure partial 16q duplications are incomplete because many individuals die during the perinatal period. We describe the clinical features of a 47-month-old Brazilian girl with 16q21q24.1 duplication. To the best of our knowledge, she is the first person with this specific chromosome segment duplication, and we compare her phenotype with the only reported individual alive with intermediate–distal pure 16q duplication.

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Narrowing down the region responsible for 1q23.3q24.1 microdeletion by identifying the smallest deletion

Human Genome Variation ◽

10.1038/s41439-019-0079-1 ◽

2019 ◽

Vol 6 (1) ◽

Author(s):

Takao Hoshina ◽

Toshiyuki Seto ◽

Taro Shimono ◽

Hiroaki Sakamoto ◽

Torayuki Okuyama ◽

...

Keyword(s):

Hearing Loss ◽

Developmental Delay ◽

Clinical Features ◽

De Novo ◽

Chromosomal Microarray ◽

Distinctive Features ◽

Neurodevelopmental Delay ◽

Deletion Size ◽

The Common

Abstract Interstitial deletions of 1q23.3q24.1 are rare. Here, chromosomal microarray testing identified a de novo microdeletion of arr[GRCh37]1q23.3q24.1(164816055_165696996) × 1 in a patient with moderate developmental delay, hearing loss, cryptorchidism, and other distinctive features. The clinical features were common to those previously reported in patients with overlapping deletions. The patient’s deletion size was 881 kb—the smallest yet reported. This therefore narrowed down the deletion responsible for the common clinical features. The deleted region included seven genes; deletion of LMX1A, RXRG, and ALDH9A1 may have caused our patient’s neurodevelopmental delay.

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CACNA1A Mutation Linking Hemiplegic Migraine and Alternating Hemiplegia of Childhood

Cephalalgia ◽

10.1111/j.1468-2982.2008.01596.x ◽

2008 ◽

Vol 28 (8) ◽

pp. 887-891 ◽

Cited By ~ 34

Author(s):

B de Vries ◽

AH Stam ◽

F Beker ◽

AMJM van den Maagdenberg ◽

KRJ Vanmolkot ◽

...

Keyword(s):

Clinical Features ◽

Molecular Mechanisms ◽

De Novo ◽

Monozygotic Twin ◽

Familial Hemiplegic Migraine ◽

Hemiplegic Migraine ◽

Mutation Scanning ◽

Alternating Hemiplegia Of Childhood ◽

Neurological Phenotype ◽

Cacna1a Mutation

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

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Clinical significance of dasatinib-induced pleural effusion in patients with de novo chronic myeloid leukemia

Hematology Reports ◽

10.4081/hr.2018.7474 ◽

2018 ◽

Vol 10 (3) ◽

Cited By ~ 1

Author(s):

Aya Nakaya ◽

Shinya Fujita ◽

Atsushi Satake ◽

Takahisa Nakanishi ◽

Yoshiko Azuma ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Clinical Features ◽

Myeloid Leukemia ◽

De Novo ◽

Late Onset ◽

Molecular Response ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Treatment Agent

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

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De novo mosaic and partial monosomy of chromosome 21 in a case with superior vena cava duplication

10.21203/rs.3.rs-39199/v1 ◽

2020 ◽

Author(s):

Abul Kalam Azad ◽

Lindsay Yanakakis ◽

Samantha Issleb ◽

Jessica Turina ◽

Kelli Drabik ◽

...

Keyword(s):

Superior Vena Cava ◽

De Novo ◽

Superior Vena ◽

Vena Cava ◽

Chromosome 21 ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Chromosomal Anomalies ◽

Partial Monosomy ◽

Increased Risk

Abstract Background Full or partial monosomy of chromosome (chr) 21 is a very rare abnormal cytogenetic finding. It is characterized by variable sizes and deletion breakpoints on the long arm (q) of chr 21 that lead to a broad spectrum of phenotypes that include an increased risk of birth defects, developmental delay and intellectual deficit. Case presentation: We report a 37-year-old G1P0 woman initially screened by non-invasive prenatal testing with no positive findings that was followed by an 18-week anatomy scan with a fetal finding of duplication of the superior vena cava (SVC). The medical and family history was otherwise uneventful. After appropriate genetic counseling, amniocentesis was performed to evaluate suspected chromosomal anomalies. Conclusions Fluorescent in situ hybridization revealed loss of one chr 21 signal that was further delineated by chromosomal microarray analysis on uncultured amniocytes as a terminal 10 Mb deletion on chr 21q. Karyotype and microarrays on cultured amniocytes showed two cell lines for a mosaic 21q terminal deletion and monosomy 21. The combined molecular cytogenetics results reported as mos 45,XX,-21[10]/46,XX,del(21)(q22)dn[20].nuc ish(D21S342/D21S341/D21S259 × 1)[100].arr[GRCh37] 21q11.2q22.12(15412676_36272993)x1 ~ 2,21q22.12q22.3(36431283_47612400)x1. Parental chromosomal analysis revealed normal karyotypes. Thus, this was a de novo mosaic full and partial monosomy of chr 21 in a case with SVC duplication. Despite the association of congenital heart disease with monsomy 21 we could not find any published literature or online databases for this cytogenetic abnormality. The patient terminated the pregnancy following the abnormal molecular cytogenetic results due to the possible challenges the baby would face if carried to term.

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EIF2AK2-related Neurodevelopmental Disorder With Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Mimics Pelizaeus-Merzbacher Disease

Neurology Genetics ◽

10.1212/nxg.0000000000000539 ◽

2020 ◽

Vol 7 (1) ◽

pp. e539

Author(s):

Daniel G. Calame ◽

Meagan Hainlen ◽

Danielle Takacs ◽

Leah Ferrante ◽

Kayla Pence ◽

...

Keyword(s):

Developmental Delay ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Copy Number Variants ◽

Retrospective Chart Review ◽

Missense Variant ◽

Chromosomal Microarray ◽

Single Nucleotide Variants ◽

Pelizaeus Merzbacher Disease ◽

Delayed Myelination

ObjectiveTo demonstrate that de novo missense single nucleotide variants (SNVs) in EIF2AK2 cause a neurodevelopmental disorder with leukoencephalopathy resembling Pelizaeus-Merzbacher disease (PMD).MethodsA retrospective chart review was performed of 2 unrelated males evaluated at a single institution with de novo EIF2AK2 SNVs identified by clinical exome sequencing (ES). Clinical and radiographic data were reviewed and summarized.ResultsBoth individuals presented in the first year of life with concern for seizures and developmental delay. Common clinical findings included horizontal and/or pendular nystagmus during infancy, axial hypotonia, appendicular hypertonia, spasticity, and episodic neurologic regression with febrile viral illnesses. MRI of the brain demonstrated severely delayed myelination in infancy. A hypomyelinating pattern was confirmed on serial imaging at age 4 years for proband 1. In proband 2, repeat imaging at age 13 months confirmed persistent delayed myelination. These clinical and radiographic features led to a strong suspicion of PMD. However, neither PLP1 copy number variants nor pathogenic SNVs were detected by chromosomal microarray and trio ES, respectively. Reanalysis of trio ES identified heterozygous de novo EIF2AK2 missense variant c.290C>T (p.Ser97Phe) in proband 1 and c.326C>T (p.Ala109Val) in proband 2.ConclusionsThe autosomal dominant EIF2AK2-related leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome should be considered in the differential diagnosis for PMD and other hypomyelinating leukodystrophies (HLDs). A characteristic history of developmental regression with febrile illnesses may help distinguish it from other HLDs.

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Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Cytogenetic and Genome Research ◽

10.1159/000488692 ◽

2018 ◽

Vol 154 (4) ◽

pp. 201-208 ◽

Cited By ~ 1

Author(s):

Shu Liu ◽

Zhiqing Wang ◽

Sisi Wei ◽

Jinqun Liang ◽

Nuan Chen ◽

...

Keyword(s):

Developmental Delay ◽

Gray Matter ◽

De Novo ◽

Ring Chromosome ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Chromosome 6 ◽

Material Loss ◽

Ring Chromosome 6

Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

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A case of deletion 8q22.2q22.3 in a child with de novo balanced translocation t(1;6)

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2021.04.49-56 ◽

2021 ◽

pp. 49-56

Author(s):

М.Е. Миньженкова ◽

Ж.Г. Маркова ◽

И.В. Анисимова ◽

И.В. Канивец ◽

Н.В. Шилова

Keyword(s):

Developmental Delay ◽

De Novo ◽

Current Trend ◽

Chromosomal Microarray ◽

Congenital Defects ◽

Chromosomal Microarray Analysis ◽

Balanced Translocation ◽

Genomic Imbalance ◽

Abnormal Phenotype ◽

Balanced Translocations

Выяснение этиопатогенеза аномального фенотипа у пациентов со сбалансированными транслокациями является актуальным аспектом в современной клинической цитогенетике. Формирование аномалий развития может быть ассоциировано с наличием скрытого геномного дисбаланса как в точках разрывов, так и на хромосомах, не задействованных в перестройке. Целью данного исследования явилась этиологическая диагностика геномного дисбаланса у пациента со сбалансированной транслокацией и аномалиями развития. Для детекции геномного дисбаланса у пациента со сбалансированной транслокацией использовали хромосомный микроматричный анализ (ХМА) и FISH-исследование. У пациента со сбалансированной транслокацией при ХМА была выявлена делеция на хромосоме 8, не задействованной в транслокации. Таким образом, в статье представлен новый случай делеции 8q22.2q22.3 у пациента со сбалансированной транслокацией t(1;6) и аномалиями развития вследствие делеции. Identification of the etiopathogenesis of the abnormal phenotype in patients with balanced translocations is current trend in cytogenetic laboratories. The formation of developmental anomalies can be associated with the presence of a cryptic genomic imbalance both at breakpoints and on chromosomes not involved in rearrangements.The aim of this study is diagnostics of genomic imbalance in a patient with balanced translocation and abnormal phenotype. The case was characterized by GTG-banding, chromosomal microarray analysis and FISH diagnosis. We present a new case of deletion 8q22.2-q22.3 in child with balanced translocation t(1;6) and developmental delay/congenital defects due to deletion.

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Vesicular and uncoated Rab1-dependent cargo carriers facilitate ER to Golgi transport

Journal of Cell Science ◽

10.1242/jcs.239814 ◽

2020 ◽

Vol 133 (14) ◽

pp. jcs239814 ◽

Cited By ~ 1

Author(s):

Laura M. Westrate ◽

Melissa J. Hoyer ◽

Michael J. Nash ◽

Gia K. Voeltz

Keyword(s):

Endoplasmic Reticulum ◽

De Novo ◽

Coated Vesicle ◽

First Person ◽

Coat Proteins ◽

Animal Cells ◽

Golgi Transport ◽

Er Exit Sites ◽

Copii Vesicles ◽

Export System

ABSTRACTSecretory cargo is recognized, concentrated and trafficked from endoplasmic reticulum (ER) exit sites (ERES) to the Golgi. Cargo export from the ER begins when a series of highly conserved COPII coat proteins accumulate at the ER and regulate the formation of cargo-loaded COPII vesicles. In animal cells, capturing live de novo cargo trafficking past this point is challenging; it has been difficult to discriminate whether cargo is trafficked to the Golgi in a COPII-coated vesicle. Here, we describe a recently developed live-cell cargo export system that can be synchronously released from ERES to illustrate de novo trafficking in animal cells. We found that components of the COPII coat remain associated with the ERES while cargo is extruded into COPII-uncoated, non-ER associated, Rab1 (herein referring to Rab1a or Rab1b)-dependent carriers. Our data suggest that, in animal cells, COPII coat components remain stably associated with the ER at exit sites to generate a specialized compartment, but once cargo is sorted and organized, Rab1 labels these export carriers and facilitates efficient forward trafficking.This article has an associated First Person interview with the first author of the paper.

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A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

Case Reports in Genetics ◽

10.1155/2014/470830 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Giorgia Mandrile ◽

Eleonora Di Gregorio ◽

Alessandro Calcia ◽

Alessandro Brussino ◽

Enrico Grosso ◽

...

Keyword(s):

Clinical Features ◽

Critical Region ◽

Array Cgh ◽

De Novo ◽

Genetic Disorder ◽

Phenotypic Expression ◽

Microdeletion Syndrome ◽

Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

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