scholarly journals MNS1 variant associated with situs inversus and male infertility

2019 ◽  
Vol 28 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Joseph S. Leslie ◽  
Lettie E. Rawlins ◽  
Barry A. Chioza ◽  
Oluwaseun R. Olubodun ◽  
Claire G. Salter ◽  
...  
Keyword(s):  
Male Infertility ◽  
Situs Inversus ◽  
Autosomal Recessive ◽  
Internal Organs ◽  
Genome Wide ◽  
Whole Exome ◽  
Snp Mapping ◽  
Left Right Asymmetry ◽  
And Function ◽  
Laterality Defects

Abstract Ciliopathy disorders due to abnormalities of motile cilia encompass a range of autosomal recessive conditions typified by chronic otosinopulmonary disease, infertility, situs abnormalities and hydrocephalus. Using a combination of genome-wide SNP mapping and whole exome sequencing (WES), we investigated the genetic cause of a form of situs inversus (SI) and male infertility present in multiple individuals in an extended Amish family, assuming that an autosomal recessive founder variant was responsible. This identified a single shared (2.34 Mb) region of autozygosity on chromosome 15q21.3 as the likely disease locus, in which we identified a single candidate biallelic frameshift variant in MNS1 [NM_018365.2: c.407_410del; p.(Glu136Glyfs*16)]. Genotyping of multiple family members identified randomisation of the laterality defects in other homozygous individuals, with all wild type or MNS1 c.407_410del heterozygous carriers being unaffected, consistent with an autosomal recessive mode of inheritance. This study identifies an MNS1 variant as a cause of laterality defects and male infertility in humans, mirroring findings in Mns1-deficient mice which also display male infertility and randomisation of left–right asymmetry of internal organs, confirming a crucial role for MNS1 in nodal cilia and sperm flagella formation and function.

scholarly journals Heterotaxy in Caenorhabditis : widespread natural variation in left–right arrangement of the major organs

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150404 ◽  
Author(s):  
Melissa R. Alcorn ◽  
Davon C. Callander ◽  
Agustín López-Santos ◽  
Yamila N. Torres Cleuren ◽  
Bilge Birsoy ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Recombinant Inbred Lines ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Internal Organs ◽  
Genome Wide ◽  
A Genome ◽  
Natural Isolates ◽  
Left Right Asymmetry ◽  
Genomic Regions

Although the arrangement of internal organs in most metazoans is profoundly left–right (L/R) asymmetric with a predominant handedness, rare individuals show full (mirror-symmetric) or partial (heterotaxy) reversals. While the nematode Caenorhabditis elegans is known for its highly determinate development, including stereotyped L/R organ handedness, we found that L/R asymmetry of the major organs, the gut and gonad, varies among natural isolates of the species in both males and hermaphrodites. In hermaphrodites, heterotaxy can involve one or both bilaterally asymmetric gonad arms. Male heterotaxy is probably not attributable to relaxed selection in this hermaphroditic species, as it is also seen in gonochoristic Caenorhabditis species. Heterotaxy increases in many isolates at elevated temperature, with one showing a pregastrulation temperature-sensitive period, suggesting a very early embryonic or germline effect on this much later developmental outcome. A genome-wide association study of 100 isolates showed that male heterotaxy is associated with three genomic regions. Analysis of recombinant inbred lines suggests that a small number of loci are responsible for the observed variation. These findings reveal that heterotaxy is a widely varying quantitative trait in an animal with an otherwise highly stereotyped anatomy, demonstrating unexpected plasticity in an L/R arrangement of the major organs even in a simple animal. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

Genetic basis of human left–right asymmetry disorders

2014 ◽  
Vol 16 ◽  
Author(s):  
Hao Deng ◽  
Hong Xia ◽  
Sheng Deng
Keyword(s):  
Situs Inversus ◽  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
The Body ◽  
Disease Genes ◽  
Internal Organs ◽  
Abdominal Organs ◽  
Pathogenic Genes ◽  
Left Right Asymmetry ◽  
Reduced Penetrance

Humans and other vertebrates exhibit left–right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, includingsitus inversusandheterotaxy.Situs inversusis complete mirror-imaged arrangement of the internal organs along LR axis, whereasheterotaxyis abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved insitus inversusandheterotaxyhave been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.

scholarly journals Severe haemoptysis in a 5 year old child with Kartagener’s syndrome: case report

2020 ◽  
Vol 7 (2) ◽  
pp. 462
Author(s):  
Mohinish S. ◽  
Mallesh K. ◽  
Prashanth H. K. ◽  
Ravichandra K. R.
Keyword(s):  
Case Report ◽  
Male Infertility ◽  
Situs Inversus ◽  
Primary Ciliary Dyskinesia ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Rare Autosomal Recessive Disorder ◽  
Kartagener's Syndrome ◽  
Glue Ear ◽  
Ciliary Dyskinesia

Kartagener`s syndrome, a rare autosomal recessive disorder is a type of Primary Ciliary Dyskinesia (PCD) associated situs inversus, bronchiectasis, sinusitis and male infertility. We present a case of a 5-year-old girl who came with features of bilateral glue ear, recurrent sinusitis, recurrent hemoptysis and dextrocardia. She was diagnosed to have Kartagener`s syndrome and was evaluated for recurrent hemoptysis.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

2019 ◽  
Vol 19 (9) ◽  
pp. 683-687 ◽  
Author(s):  
Tawfiq Froukh ◽  
Ammar Hawwari
Keyword(s):  
Strong Evidence ◽  
Autosomal Recessive ◽  
Eye Diseases ◽  
Initial Reaction ◽  
Genetic Contribution ◽  
Loss Of Function ◽  
Consanguineous Family ◽  
Truncated Protein ◽  
Threonine Residue ◽  
Whole Exome

Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. Result: GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

scholarly journals Robotic-assisted proximal gastrectomy using the double-flap technique for early gastric cancer with situs inversus totalis: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Atsushi Takeno ◽  
Toru Masuzawa ◽  
Shinsuke Katsuyama ◽  
Kohei Murakami ◽  
Kenji Kawai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Situs Inversus ◽  
Autosomal Recessive ◽  
Intraoperative Complications ◽  
Proximal Gastrectomy ◽  
Situs Inversus Totalis ◽  
Upper Body ◽  
Robot Assisted ◽  
Case Presentation ◽  
First Case

Abstract Background The robotic system has been applied in the treatment of gastric cancer (GC), and the procedure has been found to be safe and feasible. Situs inversus totalis (SIT) is a relatively rare autosomal recessive congenital anomaly. We successfully performed robot-assisted proximal gastrectomy (RAPG) and handsewn double-flap esophagogastrostomy for GC in a patient with SIT. Case presentation A 71-year-old woman was referred to us with an asymptomatic ulcerative lesion in the upper body of the stomach. Computed tomography revealed that she had SIT. She was diagnosed with cT1bN0M0, cStageIA gastric cancer. RAPG with lymph node dissection and handsewn double-flap esophagogastrostomy was performed. Robotic surgery enabled the surgeon to perform the surgery without changing his position and experiencing any confusion resulting from the patient’s reversed anatomy. It took 448 min, and no intraoperative complications occurred. Her postoperative course was uneventful; she was discharged on postoperative day 10. The final pathologic report showed pT1b1N0M0, pStage IA. Conclusions This is the first case describing RAPG with handsewn double-flap esophagogastrostomy for a SIT patient with early GC.

scholarly journals The genetic architecture of structural left–right asymmetry of the human brain

2021 ◽  
Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Amaia Carrion-Castillo ◽  
Marc Joliot ◽  
Bernard Mazoyer ◽  
...  
Keyword(s):  
Brain Asymmetry ◽  
Functional Enrichment ◽  
Brain Organization ◽  
Genome Wide ◽  
Brain Expression ◽  
Using Data ◽  
Left Right Asymmetry ◽  
The Uk ◽  
Subcortical Volume

AbstractLeft–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left–right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.

Sign in / Sign up

Export Citation Format

Share Document