Genotype and phenotype variability in Sj ögren‐Larsson syndrome
We describe the broad, heterogenic spectrum of phenotypes among SLS patients, which is caused by patient ‐to‐patient variability in combination with inconsistent reporting in literature. Furthermore, based on these data we established a set of guidelines that will ensure comprehensive SLS patient reporting in the future. AbstractThe Sj ögren–Larsson syndrome (SLS) is a rare autosomal recessive disorder caused by pathogenic variants in theALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). FALDH prevents the accumulation of toxic fatty aldehydes by converting them into fatty acids. PathogenicALDH3A2 v...
Source: Human Mutation - November 26, 2018 Category: Genetics & Stem Cells Authors: Maximilian Weustenfeld,
Reiner Eidelpes,
Matthias Schmuth,
William B. Rizzo,
Johannes Zschocke,
Markus A. Keller Tags: DATABASES Source Type: research
Evidence of predisposing epimutation in retinoblastoma
In conclusion, we documented that promoter methylation mimics the effect of an inactivating mutation and phenocopies RB onset. AbstractRetinoblastoma (RB), which represents the most common childhood eye cancer, is caused by biallelic inactivation ofRB1 gene. Promoter hypermethylation is quite frequent in RB tissues but conclusive evidence of soma ‐wide predisposing epimutations is currently scant. Here, 50 patients who tested negative forRB1 germline sequence alterations were screened for aberrant promoter methylation using methylation ‐specific MLPA. The assay, performed on blood, identified a sporadic patient with me...
Source: Human Mutation - November 26, 2018 Category: Genetics & Stem Cells Authors: Elisa Gelli,
Anna Maria Pinto,
Serena Somma,
Valentina Imperatore,
Marta G. Cannone,
Theodora Hadjistilianou,
Sonia Francesco,
Daniela Galimberti,
Aurora Curr ò,
Mirella Bruttini,
Francesca Mari,
Alessandra Renieri,
Francesca Ariani Tags: BRIEF REPORT Source Type: research
Genotype and phenotype variability in Sj ögren‐Larsson syndrome
We describe the broad, heterogenic spectrum of phenotypes among SLS patients, which is caused by patient ‐to‐patient variability in combination with inconsistent reporting in literature. Furthermore, based on these data we established a set of guidelines that will ensure comprehensive SLS patient reporting in the future. AbstractThe Sj ögren–Larsson syndrome (SLS) is a rare autosomal recessive disorder caused by pathogenic variants in theALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). FALDH prevents the accumulation of toxic fatty aldehydes by converting them into fatty acids. PathogenicALDH3A2 v...
Source: Human Mutation - November 26, 2018 Category: Genetics & Stem Cells Authors: Maximilian Weustenfeld,
Reiner Eidelpes,
Matthias Schmuth,
William B. Rizzo,
Johannes Zschocke,
Markus A. Keller Tags: DATABASES Source Type: research
Construction of cloning ‐friendly minigenes for mammalian expression of full‐length human NF1 isoforms
Cloning ‐friendly Human NF1 mini‐genes for expression of the full‐length type 1 and 2 isoforms have been constructed and the functionality has been validated. Together with the highly efficient knockdown construct, they are the new toolkit for NF1 research. AbstractThe neurofibromatosis type 1 (NF1) tumor suppressor gene is one of the most frequently mutated genes in human tumors. Research on the NF1 proteins has been partially hindered by the difficulties in cloning and propagating the full ‐length coding cDNAs. We have now established a condition for propagating the natural open reading frames (ORFs) and have ass...
Source: Human Mutation - November 24, 2018 Category: Genetics & Stem Cells Authors: Yan Cui,
Helen Morrison Tags: BRIEF REPORT Source Type: research
In silico and in vivo models for Qatari ‐specific classical homocystinuria as basis for development of novel therapies
Homocystinuria prevalence is high in Qatar (1:1,800) due to a founder Qatari missense mutation, c.1006C>T; p.R336C (p.Arg336Cys), in the CBS protein. Protein modeling suggest that p.R336C induces severe conformational changes; a large shift in the secondary structure, increasing the intramolecular H ‐bonds, and enlargement in the mutational spot (due to reduction of formed H‐bond around cysteine) that appears like a cavity. Consequently, these changes leads to reduce the CBS stability and activity. Our yeast and cell culture models confirmed these observations. AbstractHomocystinuria is a rare inborn error of methio...
Source: Human Mutation - November 23, 2018 Category: Genetics & Stem Cells Authors: Hesham M. Ismail,
Navaneethakrishnan Krishnamoorthy,
Nader Al ‐Dewik,
Hatem Zayed,
Nura A. Mohamed,
Valeria Di Giacomo,
Sapna Gupta,
Johannes Häberle,
Beat Thöny,
Henk J. Blom,
Waren D. Kruger,
Tawfeg Ben‐Omran,
Gheyath K. Nasrallah Tags: RESEARCH ARTICLE Source Type: research
Small supernumerary marker chromosomes: A legacy of trisomy rescue?
Possible fates of the supernumerary chromosome present in a trisomic zygote, as a consequence of partial trisomic rescue. After anaphase lagging and massive shattering in the context of a chromothripsis event, the saved portion(s) of the supernumerary chromosome may lead to a final karyotype with a small supernumerary marker chromosome (sSMC), or with 46 chromosomes and a de novo unbalanced translocation or a de novo unbalanced insertional translocation. AbstractWe studied by a whole genomic approach and trios genotyping, 12de novo, nonrecurrent small supernumerary marker chromosomes (sSMC), detected as mosaics during pre ...
Source: Human Mutation - November 22, 2018 Category: Genetics & Stem Cells Authors: Nehir Edibe Kurtas,
Luciano Xumerle,
Lorena Leonardelli,
Massimo Delledonne,
Alfredo Brusco,
Krystyna Chrzanowska,
Albert Schinzel,
Daniela Larizza,
Silvana Guerneri,
Federica Natacci,
Maria Clara Bonaglia,
Paolo Reho,
Emmanouil Manolakos,
Te Tags: BRIEF REPORT Source Type: research
EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome
This article is protected by copyright. All rights reserved (Source: Human Mutation)
Source: Human Mutation - November 21, 2018 Category: Genetics & Stem Cells Authors: Sagar J. Pathak,
James L. Mueller,
Kevin Okamoto,
Barun Das,
Jozef Hertecant,
Lynn Greenhalgh,
Trevor Cole,
Vered Pinsk,
Baruch Yerushalmi,
Odul E. Gurkan,
Michael Yourshaw,
Erick Hernandez,
Sandy Oesterreicher,
Sandhia Naik,
Ian R. Sanderso Tags: MUTATION UPDATE Source Type: research
Mutational and Phenotypic Spectra of KCNE1 deficiency in Jervell and Lange ‐Nielsen Syndrome and Romano‐Ward Syndrome
This article is protected by copyright. All rights reserved (Source: Human Mutation)
Source: Human Mutation - November 21, 2018 Category: Genetics & Stem Cells Authors: Rabia Faridi,
Risa Tona,
Alessandra Brofferio,
Michael Hoa,
Rafal Olszewski,
Isabelle Schrauwen,
Muhammad Z.K. Assir,
Akhtar A. Bandesha,
Asma A. Khan,
Atteeq U. Rehman,
Carmen Brewer,
Wasim Ahmed,
Suzanne M. Leal,
Sheikh Riazuddin,
Steven E Tags: MUTATION UPDATE Source Type: research
EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome
This article is protected by copyright. All rights reserved (Source: Human Mutation)
Source: Human Mutation - November 21, 2018 Category: Genetics & Stem Cells Authors: Sagar J. Pathak,
James L. Mueller,
Kevin Okamoto,
Barun Das,
Jozef Hertecant,
Lynn Greenhalgh,
Trevor Cole,
Vered Pinsk,
Baruch Yerushalmi,
Odul E. Gurkan,
Michael Yourshaw,
Erick Hernandez,
Sandy Oesterreicher,
Sandhia Naik,
Ian R. Sanderso Tags: MUTATION UPDATE Source Type: research
Mutational and Phenotypic Spectra of KCNE1 deficiency in Jervell and Lange ‐Nielsen Syndrome and Romano‐Ward Syndrome
This article is protected by copyright. All rights reserved (Source: Human Mutation)
Source: Human Mutation - November 21, 2018 Category: Genetics & Stem Cells Authors: Rabia Faridi,
Risa Tona,
Alessandra Brofferio,
Michael Hoa,
Rafal Olszewski,
Isabelle Schrauwen,
Muhammad Z.K. Assir,
Akhtar A. Bandesha,
Asma A. Khan,
Atteeq U. Rehman,
Carmen Brewer,
Wasim Ahmed,
Suzanne M. Leal,
Sheikh Riazuddin,
Steven E Tags: MUTATION UPDATE Source Type: research
Disease ‐causing variants of the conserved +2T of 5′ splice sites can be rescued by engineered U1snRNAs
The ability of variants of the spliceosomal U1snRNA to rescue splicing has been proven in several human disease models, but not for nucleotide changes at the conserved GT nucleotide of 5 ′ splice sites (5′ss), frequent and associated with severe phenotypes. Through minigene expression of variants at the 5′ss ofF9 intron 3 and splicing modulation by engineered U1snRNAs, we demonstrated that some nucleotide changes at the 5 ′ss +2T nucleotide can be rescued, thus expanding the applicability of this U1snRNA‐based approach. AbstractThe ability of variants of the spliceosomal U1snRNA to rescue splicing has been proven...
Source: Human Mutation - November 19, 2018 Category: Genetics & Stem Cells Authors: Daniela Scalet,
Iva Maestri,
Alessio Branchini,
Francesco Bernardi,
Mirko Pinotti,
Dario Balestra Tags: BRIEF REPORT Source Type: research
Early infantile ‐onset epileptic encephalopathy 28 due to a homozygous microdeletion involving the WWOX gene in a region of uniparental disomy
This report describes a rare autosomal recessive disorder with multiple genetic etiologies, one that involves uniparental disomy. A 6 ‐year‐old girl was admitted to the NIH Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, facial dysmorphisms, and skeletal abnormalities. Chromosome 16q22.1–16q24.3 uniparental disomy, included a maternally inherited homozygous microdeletion coveri ng exon 6 ofWWOX (NM_016373.3), which could cause the seizures and intellectual disability. Additional pathogenic compound heterozygous variants inHSPG2 are likely responsible for the patient's s...
Source: Human Mutation - November 18, 2018 Category: Genetics & Stem Cells Authors: Mariska Davids,
Thomas Markello,
Lynne A. Wolfe,
Xenia Chepa ‐Lotrea,
Cynthia J. Tifft,
William A. Gahl,
May Christine V. Malicdan Tags: BRIEF REPORT Source Type: research
Recessive mutations in the neuronal isoforms of DST, encoding dystonin, lead to abnormal actin cytoskeleton organization and HSAN type VI
Dystonin (encoded byDST) is one of the largest proteins in humans and member of the plakin family of cytoskeleton linker protein.Mutations affecting its neuronal isoforms have been so far reported in only 2 families with highly discordant phenotypes of Hereditary Sensory and Autonomic Neuropathy (HSAN type VI).Here, we identified novel variants inDST as the genetic defects of HSAN ‐VI and contribute to its clinical and molecular definition. Functional studies showed altered cell‐motility and cytoskeletal defects providing novel pathogenic mechanisms. AbstractHereditary sensory and autonomic neuropathies (HSAN) are clin...
Source: Human Mutation - November 18, 2018 Category: Genetics & Stem Cells Authors: Paola Fortugno,
Francesco Angelucci,
Gianluca Cestra,
Letizia Camerota,
Angelo Salvatore Ferraro,
Sonia Cordisco,
Luigi Uccioli,
Daniele Castiglia,
Barbara Angelis,
Ingo Kurth,
Uwe Kornak,
Francesco Brancati Tags: RESEARCH ARTICLE Source Type: research
Early infantile ‐onset epileptic encephalopathy 28 due to a homozygous microdeletion involving the WWOX gene in a region of uniparental disomy
This report describes a rare autosomal recessive disorder with multiple genetic etiologies, one that involves uniparental disomy. A 6 ‐year‐old girl was admitted to the NIH Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, facial dysmorphisms, and skeletal abnormalities. Chromosome 16q22.1–16q24.3 uniparental disomy, included a maternally inherited homozygous microdeletion coveri ng exon 6 ofWWOX (NM_016373.3), which could cause the seizures and intellectual disability. Additional pathogenic compound heterozygous variants inHSPG2 are likely responsible for the patient's s...
Source: Human Mutation - November 18, 2018 Category: Genetics & Stem Cells Authors: Mariska Davids,
Thomas Markello,
Lynne A. Wolfe,
Xenia Chepa ‐Lotrea,
Cynthia J. Tifft,
William A. Gahl,
May Christine V. Malicdan Tags: BRIEF REPORT Source Type: research
