Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

We aimed to understand the etiology behind the abnormal craniofacial contour and other clinical presentations in a number of children with Robinow syndrome. Seven children with Robinow syndrome were enrolled in this study (autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22, and the autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14). In the autosomal recessive (AR) group, the main clinical presentations were intellectual, disability, poor schooling achievement, episodes of headache/migraine, and poor fine motor coordinative skills, in addition to massive restrictions of the spine biomechanics causing effectively the development of kyposcoliosis and frequent bouts of respiratory infections. Three-dimensional reconstruction computed tomography scan revealed early closure of the metopic and the squamosal sutures of skull bones. Massive spinal malsegmentation and unsegmented spinal bar were noted in the AR group. In addition to severe mesomelia and camptodactyly, in the autosomal dominant (AD) group, no craniosynostosis but few Wormian bones and the spine showed limited malsegemetation, and no mesomelia or camptodactyly have been noted. We wish to stress that little information is available in the literature regarding the exact pathology of the cranial bones, axial, and appendicular malformations in correlation with the variable clinical presentations in patients with the 2 types of Robinow syndrome.

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Case Report: First Occurrence of Plasmablastic Lymphoma in Activated Phosphoinositide 3-Kinase δ Syndrome

Frontiers in Immunology ◽

10.3389/fimmu.2021.813261 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zexi Yin ◽

Xin Tian ◽

Runying Zou ◽

Xiangling He ◽

Keke Chen ◽

...

Keyword(s):

Autosomal Dominant ◽

Respiratory Infections ◽

Plasmablastic Lymphoma ◽

Heterozygous Mutation ◽

Recurrent Respiratory Infections ◽

Whole Exome ◽

First Occurrence ◽

Phosphoinositide 3 Kinase ◽

Secondary Tumours

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by acquired gene function mutation (GOF). APDS has a variety of clinical phenotypes, particularly recurrent respiratory infections and lymphoproliferation. Here we report a pediatric patient with APDS who presented with recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, bronchoscopy suggesting numerous nodular protrusions in the airways and a decrease in both T and B lymphocytes, and progression to plasmablastic lymphoma (PBL) after 1 year. Whole exome sequencing revealed a heterozygous mutation in the PIK3CD gene (c.3061 G>A p.E1021K). This is the first reported case of APDS combined with PBL and pediatricians should follow up patients with APDS regularly to be alert for secondary tumours.

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Nail-Patella Syndrome

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475415588659 ◽

2015 ◽

Vol 19 (6) ◽

pp. 595-599 ◽

Cited By ~ 2

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.

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One gene, two phenotypes:ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B

Human Mutation ◽

10.1002/humu.10233 ◽

2003 ◽

Vol 22 (1) ◽

pp. 1-11 ◽

Cited By ~ 64

Author(s):

Ali R. Afzal ◽

Steve Jeffery

Keyword(s):

Autosomal Recessive ◽

Autosomal Dominant ◽

Type B ◽

Robinow Syndrome

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Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented?

Seminars in Nephrology ◽

10.1053/snep.2001.24937 ◽

2001 ◽

Vol 21 (5) ◽

pp. 430-440 ◽

Cited By ~ 23

Author(s):

Ira D. Davis ◽

Katherine MacRae Dell ◽

William E. Sweeney ◽

Ellis D. Avner

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Polycystic Kidney

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A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia

Heart Rhythm ◽

10.1016/j.hrthm.2016.05.004 ◽

2016 ◽

Vol 13 (8) ◽

pp. 1652-1660 ◽

Cited By ~ 31

Author(s):

Belinda Gray ◽

Richard D. Bagnall ◽

Lien Lam ◽

Jodie Ingles ◽

Christian Turner ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Autosomal Dominant ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Heterozygous Mutation

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ANK3 related neurodevelopmental disorders: expanding the spectrum of heterozygous loss-of-function variants

Neurogenetics ◽

10.1007/s10048-021-00655-4 ◽

2021 ◽

Author(s):

Katja Kloth ◽

Bernarda Lozic ◽

Julia Tagoe ◽

Mariëtte J. V. Hoffer ◽

Amelie Van der Ven ◽

...

Keyword(s):

Autosomal Recessive ◽

Neuronal Development ◽

Autosomal Dominant ◽

Tissue Expression ◽

Autism Spectrum ◽

Loss Of Function ◽

Ankyrin G ◽

Phenotypic Spectrum ◽

And Function ◽

Neurodevelopmental Phenotype

AbstractANK3 encodes multiple isoforms of ankyrin-G, resulting in variegated tissue expression and function, especially regarding its role in neuronal development. Based on the zygosity, location, and type, ANK3 variants result in different neurodevelopmental phenotypes. Autism spectrum disorder has been associated with heterozygous missense variants in ANK3, whereas a more severe neurodevelopmental phenotype is caused by isoform-dependent, autosomal-dominant, or autosomal-recessive loss-of-function variants. Here, we present four individuals affected by a variable neurodevelopmental phenotype harboring a heterozygous frameshift or nonsense variant affecting all ANK3 transcripts. Thus, we provide further evidence of an isoform-based phenotypic continuum underlying ANK3-associated pathologies and expand its phenotypic spectrum.

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A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

Translational Stroke Research ◽

10.1007/s12975-021-00926-0 ◽

2021 ◽

Author(s):

Qing Li ◽

Chengfeng Wang ◽

Wei Li ◽

Zaiqiang Zhang ◽

Shanshan Wang ◽

...

Keyword(s):

Basement Membrane ◽

Skin Biopsy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Dominant ◽

Chinese Family ◽

Heterozygous Mutation ◽

Collagen Type Iv ◽

Lacunar Infarcts ◽

Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

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Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽

10.1182/blood.v100.2.692 ◽

2002 ◽

Vol 100 (2) ◽

pp. 692-694 ◽

Cited By ~ 113

Author(s):

Daniel F. Wallace ◽

Palle Pedersen ◽

Jeannette L. Dixon ◽

Peter Stephenson ◽

Jeffrey W. Searle ◽

...

Keyword(s):

Iron Transport ◽

Autosomal Recessive ◽

Iron Homeostasis ◽

Autosomal Dominant ◽

Novel Mutation ◽

Hfe Gene ◽

Excess Iron ◽

Chromosome 1Q ◽

Australian Family ◽

Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

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Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel missense mutation in AVP gene in a large Italian kindred

Endocrine ◽

10.1007/s12020-021-02830-x ◽

2021 ◽

Author(s):

Carlotta Marzocchi ◽

Silvia Cantara ◽

Alfonso Sagnella ◽

Maria Grazia Castagna ◽

Marco Capezzone

Keyword(s):

Diabetes Insipidus ◽

Missense Mutation ◽

Autosomal Dominant ◽

Three Dimensional ◽

Rare Condition ◽

Central Diabetes Insipidus ◽

Disulfide Bridges ◽

Italian Family ◽

Avp Gene

Abstract Purpose Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body’s level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants. Methods In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene. Results We identified a heterozygous missense mutation (c.154 T > A; p.C52S) in AVP gene in all affected members studied of a large Italian family. In silico tools were used to investigate the pathogenic role of the mutation and three-dimensional protein structure predicted that the p.C52S impairs disulfide bridges formation resulting in misfolding of the protein. Conclusions This is the first study that identified a novel missense p.C52S mutation as causative of central diabetes insipidus in a large Italian pedigree.

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