778 results match your criteria cosegregation analysis

A Rare Variation in the 3' Untranslated Region of the Presenilin 2 Gene Is Linked to Alzheimer's Disease.

Mol Neurobiol 2021 May 19. Epub 2021 May 19.

Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100000, China.

Rare variations in coding regions may alter the amino acid sequence and function of presenilins (PSENs), which results in the dysfunction of gamma-secretase, in turn contributing to the development of familial Alzheimer's disease (AD). However, whether rare variations in the 3' untranslated region (UTR) may change the expression level of PSEN2 leading to AD remains unclear. In a familial AD pedigree, DNA samples of the patients were screened for APP, PSEN1, and PSEN2 gene mutations using Sanger sequencing. Read More

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Genetic Characterization of Mutations Related to Conidiophore Stalk Length Development in Laboratory Strain N402.

Front Genet 2021 20;12:666684. Epub 2021 Apr 20.

Institute of Biology Leiden, Microbial Sciences, Leiden University, Leiden, Netherlands.

is an important filamentous fungus in industrial biotechnology for the production of citric acid and enzymes. In the late 1980s, the N400/NRRL3 strain was selected for both fundamental and applied studies in relation to several processes including gluconic acid and protein production. To facilitate handling of , the N400 wild-type strain was UV mutagenized in two consecutive rounds to generate N401 and N402. Read More

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A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome.

Cleft Palate Craniofac J 2021 Apr 28:10556656211010909. Epub 2021 Apr 28.

Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, Guangdong, China.

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family.

Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Read More

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Whole exome sequencing analysis identifies novel Stargardt disease-related gene mutations in Chinese Stargardt disease and retinitis pigmentosa patients.

Eye (Lond) 2021 Apr 12. Epub 2021 Apr 12.

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China.

Objectives: To delineate the disease-causing mutations of the Stargardt disease-related genes in Chinese patients diagnosed with Stargardt disease or retinitis pigmentosa (RP) by whole exome sequencing analysis.

Methods: A total of 123 sporadic RP or Stargardt disease patients and 2 Stargardt disease families were recruited. All sporadic patients and the probands of the families were subjected to whole exome sequencing analysis. Read More

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A novel homozygous splice-site mutation in SCARB2 is associated with progressive myoclonic epilepsy with renal failure.

Neurol Sci 2021 Mar 26. Epub 2021 Mar 26.

Department of Medical Genetics, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, 7616914115, Iran.

Background: Progressive myoclonic epilepsy-4 with or without renal failure (EPM4) is a rare neurological autosomal recessive disorder caused by mutations in SCARB2 gene. In this study, we described clinical features and genetic causes of an Iranian family with two affected individuals whose clinical manifestations closely resembled progressive myoclonus epilepsy.

Methods: Our proband was a 38-year-old male with a history of tremor, generalized seizures, action myoclonus, ataxia, and dysarthria that presumptive diagnosed as progressive myoclonus epilepsy. Read More

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Fine Mapping and Identification of , a Lethal Gene That Regulates the PSII Repair Cycle in .

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

National Center of Rapeseed Improvement, National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

Photosystem II (PSII) is an important component of the chloroplast. The PSII repair cycle is crucial for the relief of photoinhibition and may be advantageous when improving stress resistance and photosynthetic efficiency. Lethal genes are widely used in the efficiency detection and method improvement of gene editing. Read More

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February 2021

Mutation screening and burden analysis of GLT8D1 in Chinese patients with amyotrophic lateral sclerosis.

Neurobiol Aging 2021 May 22;101:298.e17-298.e21. Epub 2020 Oct 22.

Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

The glycosyltransferase 8 domain containing 1 (GLT8D1) gene was identified to be an amyotrophic lateral sclerosis (ALS)-causative gene via pedigree cosegregation and burden analysis. In the present study, 977 Chinese sporadic ALS (sALS) cases and 47 Chinese familial ALS (fALS) cases underwent whole-exome sequencing. Rare variants with minor allele frequency <0. Read More

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Retinal Phenotype of Patients With Isolated Retinal Degeneration Due to CLN3 Pathogenic Variants in a French Retinitis Pigmentosa Cohort.

JAMA Ophthalmol 2021 03;139(3):278-291

Sorbonne Université, INSERM, Centre national de la recherche scientifique, Institut de la Vision, Paris, France.

Importance: Biallelic variants in CLN3 lead to a spectrum of diseases, ranging from severe neurodegeneration with retinal involvement (juvenile neuronal ceroid lipofuscinosis) to retina-restricted conditions.

Objective: To provide a detailed description of the retinal phenotype of patients with isolated retinal degeneration harboring biallelic CLN3 pathogenic variants and to attempt a phenotype-genotype correlation associated with this gene defect.

Design, Setting, And Participants: This retrospective cohort study included patients carrying biallelic CLN3 variants extracted from a cohort of patients with inherited retinal disorders (IRDs) investigated at the National Reference Center for Rare Ocular Diseases of the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts from December 2007 to August 2020. Read More

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Clinical diagnosis of neurofibromatosis type I in multiple family members due to cosegregation of a unique balanced translocation with disruption of the NF1 locus: Testing considerations for accurate diagnosis.

Am J Med Genet A 2021 04 8;185(4):1222-1227. Epub 2021 Jan 8.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that causes a predisposition to develop tumors along the peripheral nervous system. The NF1 gene, located at 17q11.2, has the highest mutation rate among known human genes and about half of NF1 patients have de novo pathogenic variants. Read More

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Coexistence of Meesmann Corneal Dystrophy and a Pseudo-Unilateral Lattice Corneal Dystrophy in a Patient With a Novel Pathogenic Variant in the Keratin K3 Gene: A Case Report.

Cornea 2021 Mar;40(3):370-372

Fundació de Recerca de l'Institut de Microcirurgia Ocular, Barcelona, Spain.

Purpose: This study aims to clinically and genetically report a case of coexisting Meesmann corneal dystrophy (MECD) and pseudo-unilateral lattice corneal dystrophy (LCD).

Methods: Clinical characterization was supported by a complete ophthalmological evaluation, including visual acuity measurement and slit-lamp examination. Molecular diagnosis was performed by whole-exome sequencing analyzing the gelsolin, keratin K3 (KRT3), keratin K12, and transforming growth factor-beta-induced genes. Read More

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[A novel mutation of SCN4A gene causes hypokalemic periodic paralysis in a Chinese family].

Zhonghua Yi Xue Za Zhi 2020 Dec;100(45):3622-3625

Department of Neurology, the People's Hospital of Anyang City, Anyang 455000, China.

To report a Chinese family with hypokalemic periodic paralysis (HOKPP) and investigate the clinical and pathogenic gene characteristics of the family. The clinical, electrophysiological and pathological data of the proband of the family were analyzed, and the information of the family was investigated in detail. The peripheral venous blood of the six members of the family was collected and their genomic DNA was extracted. Read More

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December 2020

The Novel Desmin Variant p.Leu115Ile Is Associated With a Unique Form of Biventricular Arrhythmogenic Cardiomyopathy.

Can J Cardiol 2021 Jun 5;37(6):857-866. Epub 2020 Dec 5.

Institute of Cardiovascular Science, University College London, London, United Kingdom; Inherited Cardiovascular Disease Unit, St Bartholomew's Hospital, London, United Kingdom.

Background: Arrhythmogenic cardiomyopathy (AC) is a heritable myocardial disorder and a major cause of sudden cardiac death. It is typically caused by mutations in desmosomal genes. Desmin gene (DES) variants have been previously reported in AC but with insufficient evidence to support their pathogenicity. Read More

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Approaching the genetic dissection of indirect adventitious organogenesis process in tomato explants.

Plant Sci 2021 Jan 16;302:110721. Epub 2020 Oct 16.

Instituto de Biología Molecular y Celular de Plantas (UPV-CSIC), Universitat Politècnica de València, Ingeniero Fausto Elio s/n, 46011, Valencia, Spain. Electronic address:

The screening of 862 T-DNA lines was carried out to approach the genetic dissection of indirect adventitious organogenesis in tomato. Several mutants defective in different phases of adventitious organogenesis, namely callus growth (tdc-1), bud differentiation (tdb-1, -2, -3) and shoot-bud development (tds-1) were identified and characterized. The alteration of the TDC-1 gene blocked callus proliferation depending on the composition of growth regulators in the culture medium. Read More

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January 2021

A Novel Locus and Candidate Gene for Familial Developmental Dyslexia on Chromosome 4q.

Z Kinder Jugendpsychiatr Psychother 2020 Nov;48(6):478-489

Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.

Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Read More

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November 2020

Identification of a Novel Variant of in a Chinese Family with Nonsyndromic Cleft Lip and Palate.

Biomed Res Int 2020 23;2020:8790531. Epub 2020 Oct 23.

School of Life Sciences, Central South University, Changsha, China.

Background: Cleft lip with or without cleft palate (CL/P) is the most common facial birth defect, with a worldwide incidence of 1 in 700-1000 live births. CL/P can be divided into syndromic CL/P (SCL/P) and nonsyndromic CL/P (NSCL/P). Genetic factors are an important component to the etiology of NSCL/P. Read More

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Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town.

Arterioscler Thromb Vasc Biol 2021 02 5;41(2):934-943. Epub 2020 Nov 5.

Division of Chemical Pathology, Department of Pathology (G.A.E.S., A.D.M.), University of Cape Town, South Africa.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor () mutations account for >90% of cases, apolipoprotein B () mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 () gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays. Read More

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February 2021

A Novel Mutation of the Gene Adversely Affects Plant Architecture in Rice ( L.).

Int J Mol Sci 2020 Oct 30;21(21). Epub 2020 Oct 30.

California Cooperative Rice Research Foundation, Inc., Biggs, CA 95917, USA.

Plant architecture is critical for enhancing the adaptability and productivity of crop plants. Mutants with an altered plant architecture allow researchers to elucidate the genetic network and the underlying mechanisms. In this study, we characterized a novel rice mutant with short height, small panicle, and narrow and thick deep green leaves that was identified from a cross between a rice cultivar and a weedy rice accession. Read More

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October 2020

A novel homozygous variant in an Iranian pedigree with cerebellar ataxia, mental retardation, and dysequilibrium syndrome type 4.

J Clin Lab Anal 2020 Nov 17;34(11):e23484. Epub 2020 Jul 17.

Department of Paediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Cerebellar ataxia, mental retardation, and dysequilibrium (CAMRQ) syndrome is a rare and early-onset neurodevelopmental disorder. Four subtypes of this syndrome have been identified, which are clinically and genetically different. To date, altogether 32 patients have been described with ATP8A2 mutations and phenotypic features assigned to CAMRQ type 4. Read More

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November 2020

Analysis of indigenous plasmid sequences of DS002 reveals the existence of lateral mobility and extensive genetic recombination among plasmids.

J Genet 2020 ;99

Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.

Genome sequence of DS002 revealed the existence of seven contigs with features of indigenous plasmids. Of the seven contigs, three of them have shown size and sequence identity. They appeared to have been generated due to the unique recombination events leading to a large-scale recombination and sequence inversions. Read More

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January 2020

Mapping a Locus in Using BSA-Seq and GWAS Approaches.

Front Plant Sci 2020 19;11:1243. Epub 2020 Aug 19.

Department of Biology and Geology, Research Centers CIAIMBITAL and CeiA3, University of Almería, Almería, Spain.

The sexual expression of watermelon plants is the result of the distribution and occurrence of male, female, bisexual and hermaphrodite flowers on the main and secondary stems. Plants can be monoecious (producing male and female flowers), andromonoecious (producing male and hermaphrodite flowers), or partially andromonoecious (producing male, female, bisexual, and hermaphrodite flowers) within the same plant. Sex determination of individual floral buds and the distribution of the different flower types on the plant, are both controlled by ethylene. Read More

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Novel compound heterozygous nonsense variants, p.L150* and p.Y3565*, of the USH2A gene in a Chinese pedigree are associated with Usher syndrome type IIA.

Mol Med Rep 2020 Oct 3;22(4):3464-3472. Epub 2020 Aug 3.

Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. ChinaDepartment of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000.

Usher syndrome refers to a group of genetically and clinically heterogeneous autosomal recessive diseases with retinitis pigmentosa (RP) and hearing deficiencies. The association between Usher syndrome‑causative genes and resultant Usher syndrome phenotypes in patients are highly variable. In the present study, a Chinese family with Usher syndrome was recruited, and targeted next‑generation sequencing, Sanger sequencing and segregation analysis were performed. Read More

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October 2020

The impact of the c.5603A>T hypomorphic variant on founder mutation screening of for Stargardt disease in South Africa.

Mol Vis 2020 23;26:613-622. Epub 2020 Aug 23.

UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.

Purpose: Seven founder mutations in underlie a large proportion of Stargardt disease in the South African Caucasian population of Afrikaner descent. The Quick 7 assay was locally developed to test for these specific mutations and is available through the National Health Laboratory Service. However, in 2017 it was suggested that one of these mutations, c. Read More

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R2R3-MYB genes control petal pigmentation patterning in Clarkia gracilis ssp. sonomensis (Onagraceae).

New Phytol 2021 01 29;229(2):1147-1162. Epub 2020 Sep 29.

Department of Biology, Duke University, Durham, NC, 27708, USA.

Petal pigmentation patterning is widespread in flowering plants. The genetics of these pattern elements has been of great interest for understanding the evolution of phenotypic diversification. Here, we investigate the genetic changes responsible for the evolution of an unpigmented petal element on a colored background. Read More

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January 2021

Considerations in assessing germline variant pathogenicity using cosegregation analysis.

Genet Med 2020 12 10;22(12):2052-2059. Epub 2020 Aug 10.

University of Utah, Salt Lake City, UT, USA.

Purpose: The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have developed guidelines for classifying germline variants as pathogenic or benign to interpret genetic testing results. Cosegregation analysis is an important component of the guidelines. There are two main approaches for cosegregation analysis: meiosis counting and Bayes factor-based quantitative methods. Read More

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December 2020

A case report of an intermediate phenotype between congenital myasthenic syndrome and D-2- and L-2-hydroxyglutaric aciduria due to novel SLC25A1 variants.

BMC Neurol 2020 Jul 13;20(1):278. Epub 2020 Jul 13.

Department of Neurology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.

Background: Variants in the SLC25A1 gene are associated with a severe neurometabolic disease, D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). A report in 2014 presented the first account of congenital myasthenic syndrome (CMS) with mild intellectual disability (ID) caused by SLC25A1. To date, only two missense variants in SLC25A1 have been linked to CMS. Read More

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Whole-Exome Sequencing Identifies Three Candidate Homozygous Variants in a Consanguineous Iranian Family with Autism Spectrum Disorder and Skeletal Problems.

Mol Syndromol 2020 Jun 11;11(2):62-72. Epub 2020 Mar 11.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Autism spectrum disorder (ASD) is characterized by 3 core symptoms with impaired social communication, repetitive behavior, and/or restricted interests in early childhood. As a complex neurodevelopmental disorder (NDD), the phenotype and severity of autism are extremely heterogeneous. Genetic factors have a key role in the etiology of autism. Read More

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A cautionary tale: Is this APOB whole-gene duplication actually pathogenic?

J Clin Lipidol 2020 Sep - Oct;14(5):631-635. Epub 2020 Jun 15.

Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

A 22-year-old woman presented with elevated low-density lipoprotein (LDL) cholesterol and clinically suspected familial hypercholesterolemia. Initial genetic analysis by Sanger sequencing found no causal variants in LDLR or other familial hypercholesterolemia genes. More than a decade later, her 9-year-old daughter was also found to have elevated LDL cholesterol. Read More

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A novel splicing pathogenic variant in COL1A1 causing osteogenesis imperfecta (OI) type I in a Chinese family.

Mol Genet Genomic Med 2020 09 25;8(9):e1366. Epub 2020 Jun 25.

The Second Hospital, Shanxi Medical University, Taiyuan, China.

Background: Osteogenesis imperfecta (OI), a rare autosomal inheritable disorder characterized by bone fragility and skeletal deformity, is caused by pathogenic variants in genes impairing the synthesis and processing of extracellular matrix protein collagen type I. With the use of next-generation sequencing and panels approaches, an increasing number of OI patients can be confirmed and new pathogenic variants can be discovered. This study sought to identify pathogenic gene variants in a Chinese family with OI I. Read More

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September 2020

The Novel Compound Heterozygous Mutations of Identified in a Family with Distal Arthrogryposis Type 5D.

Biomed Res Int 2020 23;2020:2149342. Epub 2020 May 23.

School of Life Sciences, Central South University, Changsha, China.

Introduction: Distal arthrogryposis type 5D (DA5D) is an autosomal recessive disease. The clinical symptoms include contractures of the joints of limbs, especially camptodactyly of the hands and/or feet, unilateral ptosis, a round-shaped face, arched eyebrows, and micrognathia, without ophthalmoplegia. is a DA5D causative gene that encodes a membrane-bound metalloprotease. Read More

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A Missense Mutation in IRS1 is Associated with the Development of Early-Onset Type 2 Diabetes.

Int J Endocrinol 2020 25;2020:9569126. Epub 2020 Jan 25.

Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 21 Shengli Road, 430021 Wuhan, Hubei, China.

There could be an overlap of monogenic diabetes and early-onset type 2 diabetes mellitus. Precise diagnosis of early-onset diabetes has proven valuable for understanding the mechanism of diabetes and selecting optimal therapy. The majority of maturity onset diabetes of the young (MODY) pathogenic genes in China is still unknown. Read More

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January 2020