scholarly journals Discordant phenotypes in twins with infantile nystagmus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdullah Aamir ◽  
Helen J. Kuht ◽  
Rebecca J. McLean ◽  
Gail D. E. Maconachie ◽  
Viral Sheth ◽  
...  
Keyword(s):  
Monozygotic Twins ◽  
Optokinetic Reflex ◽  
Dizygotic Twins ◽  
Infantile Nystagmus ◽  
Foveal Hypoplasia ◽  
Discordant Twins ◽  
Low Prevalence ◽  
Pupil Tracking ◽  
First Time ◽  
Generation Sequencing

AbstractInfantile nystagmus (IN) may result from aetiologies including albinism and FRMD7 mutations. IN has low prevalence, and twins with IN are rare. Whilst discordant presentation has been previously reported for IN, we present for the first time the comprehensive assessment of diagnostically discordant monozygotic twins. From a cohort of over 2000 patients, we identified twins and triplets discordant for nystagmus. Using next-generation sequencing, high-resolution infra-red pupil tracking and optical coherence tomography, we characterised differences in genotype and phenotype. Monozygotic twins (n = 1), dizygotic twins (n = 3) and triplets (n = 1) were included. The monozygotic twins had concordant TYR variants. No causative variants were identified in the triplets. Dizygotic twins had discordant variants in TYR, OCA2 and FRMD7. One unaffected co-twin demonstrated sub-clinical nystagmus. Foveal hypoplasia (FH) was noted in four of five probands. Both co-twins of the monozygotic pair and triplets displayed FH. In three families, at least one parent had FH without nystagmus. FH alone may be insufficient to develop nystagmus. Whilst arrested optokinetic reflex pathway development is implicated in IN, discordant twins raise questions regarding where differences in development have arisen. In unaffected monozygotes therefore, genetic variants may predispose to oculomotor instability, with variable expressivity possibly responsible for the discordance observed.

Association of Handedness and Birth Order in Monozygotic Twins

1979 ◽  
Vol 28 (1) ◽  
pp. 67-68 ◽  
Author(s):  
J.C. Christian ◽  
D.S. Hunter ◽  
M.M. Evans ◽  
F.M. Standeford
Keyword(s):  
Middle Class ◽  
Birth Order ◽  
Random Sample ◽  
Significant Relationship ◽  
Monozygotic Twins ◽  
Left Handed ◽  
Dizygotic Twins ◽  
Discordant Twins

In a random sample of 104 pairs of middle-class Caucasian, handedness-discordant twins six years of age or older, a significant relationship has been found between birth order and handedness in monozygotic twins, there being an excess of left-handed among first-born twins (P < 0.01). No such relation has been found in dizygotic twins.

An Unusual Phenotype in Dutch Patients With Oculocutaneous Albinism Type 4: Evident Hypopigmentation Without Other Ocular Deficits.

2021 ◽  
Author(s):  
Charlotte C Kruijt ◽  
Nicoline E Schalij-Delfos ◽  
Gerard C de Wit ◽  
Ralph F Florijn ◽  
Maria M van Genderen
Keyword(s):  
Visual Acuity ◽  
Visual Pathways ◽  
Oculocutaneous Albinism ◽  
Novel Mutations ◽  
Normal Visual Acuity ◽  
Diagnostic Center ◽  
Foveal Hypoplasia ◽  
Unusual Phenotype ◽  
First Time ◽  
Dutch Cohort

Abstract Purpose: To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4).Patients and Methods: We collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia, chiasmal misrouting, and molecular analyses of nine Dutch OCA4 patients from the Bartiméus Diagnostic Center for complex visual disorders.Results: All patients had severely reduced pigmentation of skin, hair, and eyes with iris transillumination over 360 degrees. Three unrelated OCA4 patients had normal VA, no nystagmus, no foveal hypoplasia, and no misrouting of the visual pathways. Six patients had poor visual acuity (0.6 to 1.0 logMAR), nystagmus, severe foveal hypoplasia and misrouting. We found two novel mutations in the SLC45A2 gene, c.310C>T; p.(Pro104Ser), and c.1368+3_1368+9del p.(?).Discussion: OCA4 patients of this Dutch cohort all had hypopigmentation of skin, hair, and iris translucency. However, patients were either severely affected with regard to visual acuity, foveal hypoplasia, and misrouting, or visually not affected at all. We describe for the first time OCA4 patients with an evident lack of pigmentation, but normal visual acuity, normal foveal development and absence of misrouting. This implies that absence of melanin does not invariably lead to foveal hypoplasia and abnormal routing of the visual pathways.

scholarly journals Human papillomavirus genotyping as a tool for cervical cancer prevention: from commercially available human papillomavirus DNA test to next-generation sequencing

2020 ◽  
Vol 6 (9) ◽  
pp. FSO603
Author(s):  
Tauana Christina Dias ◽  
Adhemar Longatto-Filho ◽  
Nathalia C Campanella
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Cancer Prevention ◽  
Cancer Development ◽  
Cervical Carcinogenesis ◽  
Dna Test ◽  
First Time ◽  
Papillomavirus Dna ◽  
Principal Elements ◽  
Generation Sequencing

The biological importance of human papillomavirus (HPV) in the field of medicine – related to cervical carcinogenesis – has been extensively reported in the last decades. For the first time, a direct correlation between cause and effect to explain a cancer development was completely achieved in medical research. Consequently, the Nobel Prize was awarded to HZ Hausen in 2008 for his efforts to understand the effects of persistent infection of oncogenic types of HPV and malignancy transformation. The aim of the present review was to summarize the principal elements of HPV characteristics and their importance in oncology.

Ocular Albinism

2021 ◽  
pp. 236-242
Keyword(s):  
Gene Therapy ◽  
Differential Diagnosis ◽  
Optic Nerve ◽  
Effective Treatment ◽  
Early Treatment ◽  
Loss Of Function ◽  
Poor Vision ◽  
Ocular Albinism ◽  
Infantile Nystagmus ◽  
Foveal Hypoplasia

Ocular albinism is an X-linked melanosome biogenesis disorder, leading to mild cutaneous symptoms and persistent visual impairment in affected males. As a result of mutations in the GPR143 gene, a defect occurs in the transformation of melanosomes into macromelanosomes with loss of function at the GPBR143 receptor. Clinically, manifests with nystagmus, which typically occurs in infants until the sixth month from birth. Optic nerve misdirection which can be detected by VEP is important in the differential diagnosis of another infantile nystagmus. Foveal hypoplasia is the most responsible finding for poor vision. Today, functional losses are tried to be minimized by differential diagnosis and early treatment. It is predicted that more effective treatment can be provided with gene therapy in the future.

Adipocyte-rich CTNNB1-mutated Intramuscular Gardner Fibroma Progressing to Desmoid Fibromatosis

2020 ◽  
pp. 109352662096880
Author(s):  
Andrea Bakker ◽  
Jonathan C Slack ◽  
Mara Caragea ◽  
Kyle C Kurek ◽  
Marie-Anne Bründler
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Tumor ◽  
Soft Tissue Tumors ◽  
Molecular Testing ◽  
Tissue Mass ◽  
Desmoid Fibromatosis ◽  
Benign Soft Tissue Tumor ◽  
First Time ◽  
Generation Sequencing

Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called “GF-DF sequence”) is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear β-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF–DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF–DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.

scholarly journals Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids

2020 ◽  
Vol 25 (11) ◽  
pp. 2695-2711
Author(s):  
Tomoyo Sawada ◽  
Thomas E. Chater ◽  
Yohei Sasagawa ◽  
Mika Yoshimura ◽  
Noriko Fujimori-Tonou ◽  
...  
Keyword(s):  
Single Cell ◽  
Neural Progenitor Cells ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Inhibitory Neurons ◽  
Cellular Mechanisms ◽  
Cell Type Specific ◽  
Discordant Twins ◽  
Induced Pluripotent ◽  
Human Brains

Abstract Despite extensive genetic and neuroimaging studies, detailed cellular mechanisms underlying schizophrenia and bipolar disorder remain poorly understood. Recent progress in single-cell RNA sequencing (scRNA-seq) technologies enables identification of cell-type-specific pathophysiology. However, its application to psychiatric disorders is challenging because of methodological difficulties in analyzing human brains and the confounds due to a lifetime of illness. Brain organoids derived from induced pluripotent stem cells (iPSCs) of the patients are a powerful avenue to investigate the pathophysiological processes. Here, we generated iPSC-derived cerebral organoids from monozygotic twins discordant for psychosis. scRNA-seq analysis of the organoids revealed enhanced GABAergic specification and reduced cell proliferation following diminished Wnt signaling in the patient, which was confirmed in iPSC-derived forebrain neuronal cells. Two additional monozygotic twin pairs discordant for schizophrenia also confirmed the excess GABAergic specification of the patients’ neural progenitor cells. With a well-controlled genetic background, our data suggest that unbalanced specification of excitatory and inhibitory neurons during cortical development underlies psychoses.

scholarly journals Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review

2019 ◽  
Vol 8 (5) ◽  
pp. 750 ◽  
Author(s):  
Jessica Garau ◽  
Vanessa Cavallera ◽  
Marialuisa Valente ◽  
Davide Tonduti ◽  
Daisy Sproviero ◽  
...  
Keyword(s):  
Interferon Signaling ◽  
Cerebral Calcification ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Functional Investigation ◽  
Genetically Determined ◽  
Next Generation Sequencing Ngs ◽  
First Time ◽  
Generation Sequencing ◽  
Italian Cohort

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.

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