scholarly journals Nail-Patella Syndrome

2000 ◽  
Vol 11 (9) ◽  
pp. 1762-1766 ◽  
Author(s):  
NINE V.A.M. KNOERS ◽  
ERNIE M.H.F. BONGERS ◽  
SYLVIA E.C. VAN BEERSUM ◽  
ED J.P. LOMMEN ◽  
HANS VAN BOKHOVEN ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Renal Impairment ◽  
Renal Disease ◽  
Autosomal Dominant ◽  
Family Members ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
High Incidence ◽  
Novel Variant ◽  
Nail Patella Syndrome

Abstract. Nail-patella syndrome is an autosomal dominant disorder characterized by dyplasia of finger nails, skeletal anomalies, and, frequently, renal disease. It has recently been shown that this disorder is caused by putative loss-of-function mutations in a transcription factor (LMX1B) belonging to the LIM-homeodomain family, members of which are known to be important for pattern formation during development. A cohort of eight Dutch NPS families were screened for mutations in the LMX1B gene; seven different mutations, including one novel variant, were identified. Three of the mutations are very likely to result in truncated LMX1B proteins, three are predicted to influence sequence-specific DNA binding, and one is presumed to prevent the formation of a stable protein by abolishing the Zn(II) binding site of the protein. Although there was a remarkable high incidence of renal disease in one of the families, the nephropathy was not seen in all affected family members and the severity of renal impairment varied significantly among the patients. This indicates that the incidence and severity of nephropathy within this family cannot be attributed to the LMX1B genotype. In addition, evidence of a correlation between other characteristics of the NPS phenotype and specific mutations has not been found.

scholarly journals A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype

2021 ◽  
Author(s):  
David Mengel ◽  
Andreas Traschütz ◽  
Selina Reich ◽  
Alejandra Leyva-Gutiérrez ◽  
Friedemann Bender ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
De Novo ◽  
Family Members ◽  
Start Codon ◽  
Mrna Levels ◽  
Adult Onset ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder

Abstract Background Biallelic STUB1 variants are a well-established cause of autosomal-recessive early-onset multisystemic ataxia (SCAR16). Evidence for STUB1 variants causing autosomal-dominant ataxia (SCA48) so far largely relies on segregation data in larger families. Presenting the first de novo occurrence of a heterozygous STUB1 variant, we here present additional qualitative evidence for STUB1-disease as an autosomal-dominant disorder. Methods Whole exome sequencing on an index patient with sporadic early-onset ataxia, followed by Sanger sequencing in all family members, was used to identify causative variants as well as to rule out alternative genetic hits and intronic STUB1 variants. STUB1 mRNA and protein levels in PBMCs in all family members were analysed using qRT-PCR and Western Blot. Results A previously unreported start-lost loss-of-function variant c.3G>A in the start codon of STUB1 was identified in the index case, occurring de novo and without evidence for a second (potentially missed) variant (e.g., intronic or copy number) in STUB1. The patient showed an early adult-onset multisystemic ataxia complicated by spastic gait disorder, distal myoclonus and cognitive dysfunction, thus closely mirroring the systems affected in autosomal-recessive STUB1-associated disease. In line with the predicted start-lost effect of the variant, functional investigations demonstrated markedly reduced STUB1 protein expression in PBMCs, whereas mRNA levels were intact. Conclusion De novo occurrence of the loss-of-function STUB1 variant in our case with multisystemic ataxia provides a qualitatively additional line of evidence for STUB1-disease as an autosomal-dominant disorder, in which the same neurological systems are affected as in its autosomal-recessive counterpart. Moreover, this finding adds support for loss-of-function as a mechanism underlying autosomal-dominant STUB1-disease, thus mirroring its autosomal-recessive counterpart also in terms of the underlying mutational mechanism.

Nail-Patella Syndrome

2015 ◽  
Vol 19 (6) ◽  
pp. 595-599 ◽  
Author(s):  
Najla Al-Dawsari ◽  
Ahmed Al-Mokhadam ◽  
Hind Al-Abdulwahed ◽  
Nouriya Al-Sannaa
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Anterior Segment ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Consanguineous Family ◽  
Autosomal Dominant Disorder ◽  
Nail Changes ◽  
Chromosome 9Q ◽  
Nail Patella Syndrome

Background: Nail-patella syndrome (NPS) is an autosomal dominant disorder with a variable interfamilial and intrafamilial clinical expressivity and penetrance. It is caused by loss-of-function heterozygous mutation in the LIM-homeodomain transcription factor (LMX1B) located on chromosome 9q. The pleiotropic LMB1X gene, a member of the homeogene family, is involved in the development of glomerular basement membrane, dorsoventral limb structures, along with the nails and the anterior segment of the eye. Objective: Here, we report a Saudi Arab consanguineous family with 2 affected sisters presented with the typical nail changes of NPS. Methods: DNA samples were collected from the sisters and their parents after consent. Results: Both sisters were found to be homozygous for a previously described disease-causing mutation (c.268C>T) at the (LMX1B) gene. Both of the phenotypically normal parents were confirmed to be heterozygous for the same mutation. Conclusion: This finding supports the autosomal recessive mode of inheritance in this family.

CASZ1 loss-of-function mutation contributes to familial dilated cardiomyopathy

2017 ◽  
Vol 55 (9) ◽  
Author(s):  
Xing-Biao Qiu ◽  
Xin-Kai Qu ◽  
Ruo-Gu Li ◽  
Hua Liu ◽  
Ying-Jia Xu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activity ◽  
Autosomal Dominant ◽  
Cardiac Development ◽  
Index Patient ◽  
Loss Of Function ◽  
Zinc Finger Transcription Factor ◽  
Complete Penetrance ◽  
Familial Dilated Cardiomyopathy ◽  
Postnatal Adaptation

AbstractBackground:The zinc finger transcription factor CASZ1 plays a key role in cardiac development and postnatal adaptation, and in mice, deletion of theMethods:The coding exons and splicing junction sites of theResults:A novel heterozygous CASZ1 mutation, p.K351X, was identified in an index patient with DCM. Genetic analysis of the mutation carrier’s family showed that the mutation co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The nonsense mutation, which was absent in 400 referential chromosomes, altered the amino acid that was highly conserved evolutionarily. Biological investigations revealed that the mutant CASZ1 had no transcriptional activity.Conclusions:The current study reveals

Caution in interpretation of disease causality for heterozygous loss-of-function variants in the MYH8 gene associated with autosomal dominant disorder

2017 ◽  
Vol 60 (6) ◽  
pp. 312-316 ◽  
Author(s):  
Zunyan Dai ◽  
Zachary Whitt ◽  
Lindsey C. Mighion ◽  
Alessandro Pontoglio ◽  
Lora J.H. Bean ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Disease Causality

scholarly journals Cleidocranial dysplasia. A molecular and clinical review.

2018 ◽  
Vol 8 (1) ◽  
pp. 35-38
Author(s):  
Andrea Avendaño ◽  
Francisco Cammarata-Scalisi ◽  
Mochamad Fahlevi Rizal ◽  
Sarworini Bagio Budiardjo ◽  
Margaretha Suharsini ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Autosomal Dominant ◽  
Cleidocranial Dysplasia ◽  
Supernumerary Teeth ◽  
Phenotypic Characteristics ◽  
Autosomal Dominant Disorder ◽  
Dental Abnormalities ◽  
Related Transcription Factor

Cleidocranial dysplasia (CCD) is a rare autosomal dominant disorder characterized by skeletal and dental abnormalities primarily, short stature, aplasia or hypoplasia of clavicles, open fontanelles and supernumerary teeth. Heterozygous mutations of the runt related transcription factor 2 (RUNX2) gene have been found in approximately 60-70% of cases leaving a large number of cases with no defined genetic cause which led us to delve into molecular mechanisms underlying CCD and thus to detect potential target genes to be explored in these patients. In this review we also highlight very broadly the phenotypic characteristics of previously reported patients with CCD.

Thin glomerular basement membrane nephropathy and other collagenopathies

2018 ◽  
Author(s):  
Laurence Heidet ◽  
Bertrand Knebelmann ◽  
Marie Claire Gubler
Keyword(s):  
Basement Membrane ◽  
Renal Disease ◽  
Renal Biopsy ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Increased Risk ◽  
Autosomal Dominant Fashion ◽  
Nail Patella Syndrome

The discovery of a thin glomerular basement membrane in a renal biopsy without any other abnormalities can be explained in a number of ways. This could be an early biopsy in a patient with Alport syndrome, or it could be an individual who is a carrier for an Alport gene. These carriers are at increased risk of significant renal disease in their lifetime and some have proteinuria as well as haematuria, so they can no longer be equated with the historic label of benign familial haematuria. Some families with a thin glomerular basement membrane and haematuria inherited in an autosomal dominant fashion do not appear to have linkage to COL4 genes. Others have variable renal disease that has sometimes given rise to a label of mild but autosomal dominant Alport syndrome. This territory might also attract the label basement membrane 345 collagenopathy. Other uncommon conditions affecting the glomerular basement membrane include nail patella syndrome.

scholarly journals A Report of a Novel Pathogenic Variant in a Family with Buschke–Ollendorf Syndrome

2019 ◽  
Vol 09 (01) ◽  
pp. 063-065
Author(s):  
Angita Jain ◽  
Pavalan Selvam ◽  
Herjot Atwal ◽  
Paldeep S. Atwal
Keyword(s):  
Connective Tissue ◽  
Autosomal Dominant ◽  
Comprehensive Evaluation ◽  
Single Gene ◽  
Family Members ◽  
Pathogenic Variant ◽  
Connective Tissue Disorders ◽  
Phenotype Correlation ◽  
Autosomal Dominant Disorder ◽  
Gene Testing

AbstractBuschke–Ollendorf Syndrome (BOS) is a benign autosomal dominant disorder caused by pathogenic mutations in LEMD3. Here, we describe a family diagnosed to have varied phenotypes associated with BOS. Single gene testing of LEMD3 detected a heterozygous frameshift pathogenic variant in both the affected family members. Besides the phenotypic description, this report highlights the need for a comprehensive evaluation in connective tissue disorders and the importance of genotype–phenotype correlation in BOS.

scholarly journals Neuroimaging Findings in Patients with EBF3 Mutations: Report of Two Cases

2021 ◽  
pp. 1-8
Author(s):  
Mar Jiménez de la Peña ◽  
Ana Jiménez de Domingo ◽  
Pilar Tirado ◽  
Beatriz Calleja-Pérez ◽  
Luis A. Alcaraz ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Intellectual Disability ◽  
Neurodevelopmental Disorders ◽  
Autosomal Dominant ◽  
De Novo ◽  
Diffusion Tensor ◽  
Loss Of Function ◽  
Normal Range ◽  
Early B Cell Factor ◽  
And Diffusion

Early B cell factor 3 (EBF3) is a transcription factor involved in brain development. Heterozygous, loss-of-function mutations in <i>EBF3</i> have been reported in an autosomal dominant neurodevelopmental syndrome characterized by hypotonia, ataxia, and developmental delay (sometimes described as “HADD”s). We report 2 unrelated cases with novel de novo <i>EBF3</i> mutations: c.455G&#x3e;T (p.Arg152Leu) and c.962dup (p.Tyr321*) to expand the genotype/phenotype correlations of this disorder; clinical, neuropsychological, and MRI studies were used to define the phenotype. IQ was in the normal range and diffusion tensor imaging revealed asymmetric alterations of the longitudinal fasciculus in both cases. Our results demonstrate that <i>EBF3</i> mutations can underlie neurodevelopmental disorders without intellectual disability. Long tract abnormalities have not been previously recognized and suggest that they may be an unrecognized and characteristic feature in this syndrome.

scholarly journals Behçet Disease-Like Symptoms with a Novel COPA Mutation

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
E. Anderson ◽  
J. Hatch ◽  
J. Cardinal ◽  
D. Langguth ◽  
D. Coman
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Renal Disease ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Immune Dysregulation ◽  
Autoimmune Response ◽  
Autosomal Dominant Disorder ◽  
Th17 Cytokines ◽  
Copa Syndrome

COPA syndrome is a recently described autosomal dominant disorder with key immune dysregulation caused by defects within the COPA gene. These mutations lead to endoplasmic reticulum stress and autoimmune response with upregulation of Th17 cytokines. The clinical phenotype of COPA syndrome primarily comprised pulmonary disease, arthritis, and renal disease secondary to immune dysregulation, with onset of symptoms commonly in the first decade of life. Herein, we describe a family with an attenuated Behçet-like phenotype of COPA syndrome, further expanding the phenotypic understanding of this syndrome.

scholarly journals A Rare Genetic Cause of End Stage Renal Disease- Nail Patella Syndrome

2021 ◽  
Vol 4 (4) ◽  
pp. 336-337
Author(s):  
Azhar Ali Khan ◽  
Javaria Karamat
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Early Recognition ◽  
Symptomatic Relief ◽  
Specific Treatment ◽  
Autosomal Dominant Disorder ◽  
Skeletal Complications ◽  
Stage Renal Disease ◽  
End Stage ◽  
Nail Patella Syndrome

Hereditary osteo-onchodysplasia syndrome commonly known as nail patella syndrome is an autosomal dominant disorder that manifests with skeletal abnormalities and renal disease. Its incidence is 1 in 50,000 and reported in patients all over world. The renal disease involves glomerular basement membrane (GBM) thickening and rarely proceeds to End stage renal disease (ESRD). It requires histological diagnosis with electron microscopy to differentiate from other disease associated with proteinuria. As no specific treatment is available so management involves early recognition and close  follow up for symptomatic relief of renal as well as skeletal complications. Prevention involves genetic counselling being solely helpful. This case report is of a patient diagnosed with nail patella syndrome with strong family history but rapidly progressed to ESRD and we were not able to proceed for histology.

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