The power of the Mediator complex - expanding the genetic architecture and phenotypic spectrum of MED12-related disorders.
This article is protected by copyright. All rights reserved. PMID: 30006928 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - July 13, 2018 Category: Genetics & Stem Cells Authors: Charzewska A, Maiwald R, Kahrizi K, Oehl-Jaschkowitz B, Dufke A, Lemke JR, Enders H, Najmabadi H, Tzschach A, Hachmann W, Menzel C, Bienek M, Poznański J, Nawara M, Chilarska T, Obersztyn E, Hoffman-Zacharska D, Gos M, Bal J, Kalscheuer VM Tags: Clin Genet Source Type: research

Epilepsy Genetics: current knowledge, applications and future directions.
This article is protected by copyright. All rights reserved. PMID: 29992546 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - July 10, 2018 Category: Genetics & Stem Cells Authors: Myers KA, Johnstone D, Dyment DA Tags: Clin Genet Source Type: research

Report of second case and clinical and molecular characterization of Eiken syndrome.
This report characterizes Eiken syndrome and confirms that bi-allelic hypomorphic variants in PTH1R are likely to cause this condition. PMID: 29987841 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - July 10, 2018 Category: Genetics & Stem Cells Authors: Moirangthem A, Narayanan DL, Jacob P, Nishimura G, Mortier G, Girisha KM Tags: Clin Genet Source Type: research

Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans.
Abstract As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute methanol exposure. To evaluate the role of genetic variants of enzymes involved in methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute methanol poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) th...
Source: Clinical Genetics - July 2, 2018 Category: Genetics & Stem Cells Authors: Hubacek JA, Jirsa M, Bobak M, Pelclova D, Zakharov S Tags: Clin Genet Source Type: research

Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation.
This article is protected by copyright. All rights reserved. PMID: 29938792 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 25, 2018 Category: Genetics & Stem Cells Authors: Pilch J, Koppolu AA, Walczak A, Pienkowski VAM, Biernacka A, Skiba P, Machnik-Broncel J, Gasperowicz P, Kosińska J, Rydzanicz M, Emich-Widera E, Płoski R Tags: Clin Genet Source Type: research

IL11RA-related Crouzon-like autosomal recessive craniosynostosis in ten new patients: resemblances and differences.
This article is protected by copyright. All rights reserved. PMID: 29926465 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 21, 2018 Category: Genetics & Stem Cells Authors: Brischoux-Boucher E, Trimouille A, Baujat G, Goldenberg A, Schaefer E, Guichard B, Hannequin P, Paternoster G, Baer S, Cabrol C, Weber E, Godfrin G, Lenoir M, Lacombe D, Collet C, Van Maldergem L Tags: Clin Genet Source Type: research

IFT80 mutations cause a novel complex ciliopathy phenotype with retinal degeneration.
Abstract Ciliopathies, a growing pleotropic class of diseases due to mutations in genes that play an important role in primary cilia function. These highly conserved organelles are key to cell signaling. We now know, that mutations in one gene may lead to more than one ciliopathy phenotype and that one ciliopathy phenotype may be due to mutations in more than one gene. We studied the case of a female child with a novel ciliopathy phenotype and identified two novel mutations in the gene IFT80. Previously, mutations in IFT80 have been associated with a very narrow rib cage and failure of the lungs. Bone anomalies ar...
Source: Clinical Genetics - June 20, 2018 Category: Genetics & Stem Cells Authors: Moran J, Sanderson KG, Maynes J, Vig A, Batmanabane V, Kannu P, Tavares E, Vincent A, Heon E Tags: Clin Genet Source Type: research

The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.
This article is protected by copyright. All rights reserved. PMID: 29920646 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 19, 2018 Category: Genetics & Stem Cells Authors: Ruskey JA, Zhou S, Santiago R, Franche LA, Alam A, Roncière L, Spiegelman D, Fon EA, Trempe JF, Kalia LV, Postuma RB, Dupre N, Rivard GE, Assouline S, Amato D, Gan-Or Z Tags: Clin Genet Source Type: research

Genotype-phenotype correlations of low frequency variants in the complement system in renal disease and age-related macular degeneration.
In conclusion, we observed a substantial overlap of variants between aHUS/C3G and AMD, however, there is a distinct clustering of variants within specific domains. This article is protected by copyright. All rights reserved. PMID: 29888403 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 11, 2018 Category: Genetics & Stem Cells Authors: Geerlings MJ, Volokhina EB, de Jong EK, van de Kar N, Pauper M, Hoyng CB, van den Heuvel LP, den Hollander AI Tags: Clin Genet Source Type: research

Bilateral cerebellar cysts and cerebral white matter lesions with cortical dysgenesis: Expanding the phenotype of LAMB1 gene mutations.
Abstract LAMB1 gene analysis should be considered for intellectually disabled patients with cerebellar cysts, white matter signal change, and cortical malformation. Muscular involvement is absent, in contrast to the α-dystroglycanopathy types of congenital muscular dystrophies. PMID: 29888467 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 10, 2018 Category: Genetics & Stem Cells Authors: Okazaki T, Saito Y, Hayashida T, Akaboshi S, Miyake N, Matsumoto N, Kasagi N, Adachi K, Shinohara Y, Nanba E, Maegaki Y Tags: Clin Genet Source Type: research

How do consent forms for diagnostic high-throughput sequencing address unsolicited and secondary findings? A content analysis.
This article is protected by copyright. All rights reserved. PMID: 29888485 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 10, 2018 Category: Genetics & Stem Cells Authors: Vears DF, Niemiec E, Howard HC, Borry P Tags: Clin Genet Source Type: research

GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.
This article is protected by copyright. All rights reserved. PMID: 29882329 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - June 7, 2018 Category: Genetics & Stem Cells Authors: Hengel H, Keimer R, Deigendesch W, Rieß A, Marzouqa H, Zaidan J, Bauer P, Schöls L Tags: Clin Genet Source Type: research

p.D313Y is more than just a polymorphism in Fabry disease.
PMID: 29740824 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - May 10, 2018 Category: Genetics & Stem Cells Authors: du Moulin M, Muschol N Tags: Clin Genet Source Type: research

EAST/SeSAME syndrome - review of the literature and introduction of four new Latvian patients.
Abstract EAST (Epilepsy, Ataxia, Sensorineural deafness, Tubulopathy) or SeSAME (Seizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte imbalance) syndrome is a rare autosomal recessive syndrome first described in 2009 independently by Bockenhauer and Scholl. It is caused by mutations in KCNJ10, which encodes Kir4.1, an inwardly rectifying K+ channel found in the brain, inner ear, kidney and eye. To date, 16 mutations in at least 28 patients have been reported. In this paper, we review mutations causing EAST/SeSAME syndrome, clinical manifestations in detail, and efficacy of treatment in pre...
Source: Clinical Genetics - May 3, 2018 Category: Genetics & Stem Cells Authors: Marta C, Ieva M, Inna I, Mareta A, Sandra K, Pereca J, Janis S, Dita P, Jurgis S Tags: Clin Genet Source Type: research

Atrioventricular canal defect and genetic syndromes: The unifying role of Sonic Hedgehog.
Abstract The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" demonstrated that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular gr...
Source: Clinical Genetics - May 3, 2018 Category: Genetics & Stem Cells Authors: Digilio MC, Pugnaloni F, De Luca A, Calcagni G, Baban A, Dentici ML, Versacci P, Dallapiccola B, Tartaglia M, Marino B Tags: Clin Genet Source Type: research

Discovery of four exonic and one intergenic novel susceptibility loci for leprosy.
Abstract Seven new risk coding variants have been identified through an exome-wide association study (EWAS), which studied the contributions of protein-coding variants to leprosy susceptibility. But some potential susceptibility loci were not studied in the previous EWAS study because of the project consideration. Seventeen unstudied potential susceptibility loci of the previous EWAS were validated in 3,169 cases and 9,814 controls in this study. Four disease associated exonic loci were identified: rs671 in ALDH2 (P = 2.0 × 10-20 , odds ratio (OR) = 1.35), rs13259978 in SLC7A2 (P = 1.74 × 10-8 , OR = 1...
Source: Clinical Genetics - May 3, 2018 Category: Genetics & Stem Cells Authors: Wang Z, Mi Z, Wang H, Sun L, Yu G, Fu X', Wang C, Bao F, Yue Z, Zhao Q, Wang N, Cheng X, Liu H, Zhang F Tags: Clin Genet Source Type: research

Correction to: Reassessing the clinical spectrum associated with Hereditary Leiomyomatosis and Renal Cell Carcinoma syndrome in French FH mutation carriers.
PMID: 29655270 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - April 17, 2018 Category: Genetics & Stem Cells Authors: Muller M, Guillaud-Bataille M, Richard S, Benusiglio PR Tags: Clin Genet Source Type: research

Correction to: PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing.
PMID: 29655271 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - April 17, 2018 Category: Genetics & Stem Cells Authors: Biesecker BB, Woolford SW, Klein WMP, Brothers KB, Umstead KL, Lewis KL, Biesecker LG, Han PKJ Tags: Clin Genet Source Type: research

Erratum.
Authors: PMID: 29655272 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - April 17, 2018 Category: Genetics & Stem Cells Tags: Clin Genet Source Type: research

Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins.
Abstract Heredity plays an important role in the etiology of varicose veins (VVs). However, the genetic basis underlying this condition remains poorly understood. Our aim was to replicate top association signals from genome-wide association studies (GWAS) for VVs of lower extremities using two independent datasets - our sample of ethnic Russian individuals (709 cases and 278 controls) and a large cohort of British residents from UK Biobank (10,861 cases and 397,594 controls). Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562, rs7111987, rs6062618, and rs6905288 were validated in the UK Bioban...
Source: Clinical Genetics - April 16, 2018 Category: Genetics & Stem Cells Authors: Shadrina A, Tsepilov Y, Smetanina M, Voronina E, Seliverstov E, Ilyukhin E, Kirienko A, Zolotukhin I, Filipenko M Tags: Clin Genet Source Type: research

Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP.
This study aimed to investigate the frequencies and distributions of inherited variants in PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP genes in Chinese patients with HLH. A total of 265 patients diagnosed with HLH from January 2010 to December 2016 were recruited and analyzed for the six genes. Genetic variants were observed in 87 (32.83%) patients. 36 (13.58%) exhibited variants in UNC13D, 18 (6.79%) exhibited PRF1 variants, 10 (3.77%) had variants in XIAP, 9 (3.40%) exhibited variants in STXBP2, 6 (2.26%) carried variants in SH2D1A, 1 (0.38%) had STX11 variant, and 7 (2.64%) exhibited digenic variants. Monoallelic vari...
Source: Clinical Genetics - April 14, 2018 Category: Genetics & Stem Cells Authors: Chen X, Wang F, Zhang Y, Teng W, Wang M, Nie D, Zhou X, Wang D, Zhao H, Zhu P, Liu H Tags: Clin Genet Source Type: research

Systematic reanalysis of genomic data improves quality of variant interpretation.
Abstract As genomic sequencing expands, so does our knowledge of the link between genetic variation and disease. Deeper catalogs of variant frequencies improve identification of benign variants, while sequencing affected individuals reveals disease-associated variation. Accumulation of human genetic data thus makes reanalysis a means to maximize benefits of clinical sequencing. We implemented pipelines to systematically reassess sequencing data from 494 individuals with developmental disability. Reanalysis yielded pathogenic or likely pathogenic (P/LP) variants in six individuals who initially had no P/LP variants...
Source: Clinical Genetics - April 13, 2018 Category: Genetics & Stem Cells Authors: Hiatt SM, Amaral MD, Bowling KM, Finnila CR, Thompson ML, Gray DE, Lawlor JMJ, Cochran JN, Bebin EM, Brothers KB, East KM, Kelley WV, Lamb NE, Levy SE, Lose EJ, Neu MB, Rich CA, Simmons S, Myers RM, Barsh GS, Cooper GM Tags: Clin Genet Source Type: research

Expanding the clinical spectrum of biallelic ZNF335 variants.
We describe herein two additional affected individuals with biallelic ZNF335 variants, one individual with a homozygous c.1399T>C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A>G, p.(Glu1333Gly) variants in ZNF335; with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination...
Source: Clinical Genetics - April 13, 2018 Category: Genetics & Stem Cells Authors: Stouffs K, Stergachis AB, Vanderhasselt T, Dica A, Janssens S, Vandervore L, Gheldof A, Bodamer O, Keymolen K, Seneca S, Liebaers I, Jayaraman D, Hill HE, Partlow JN, Walsh CA, Jansen AC Tags: Clin Genet Source Type: research

TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies.
We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in an infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus activating, a number of transcription factors including the mixed lineage leukemia 1 (MLL1). Taspase 1-deficient mice demonstrated early lethality, skeletal abnormalities, and growth failure, which supports a potentially causal role of TASP1 deletion in this infant. Furthermore, the infant reported here had many ...
Source: Clinical Genetics - April 6, 2018 Category: Genetics & Stem Cells Authors: Suleiman J, Mundt M, Sampath S, El-Hattab AW Tags: Clin Genet Source Type: research

Corrigendum.
Authors: PMID: 29537094 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - March 23, 2018 Category: Genetics & Stem Cells Tags: Clin Genet Source Type: research

Corrigendum.
Authors: PMID: 29537095 [PubMed - in process] (Source: Clinical Genetics)
Source: Clinical Genetics - March 23, 2018 Category: Genetics & Stem Cells Tags: Clin Genet Source Type: research

Splice-site mutations in VEGFC cause loss of function and Nonne-Milroy-like primary lymphedema.
ula M PMID: 29542815 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - March 15, 2018 Category: Genetics & Stem Cells Authors: Fastré E, Lanteigne LE, Helaers R, Giacalone G, Revencu N, Dionyssiou D, Demiri E, Brouillard P, Vikkula M Tags: Clin Genet Source Type: research

Hypercalciuria and nephrolithiasis: Expanding the renal phenotype of Donnai-Barrow syndrome.
Abstract Whole exome sequencing detected novel likely pathogenic variants in LRP2 gene in 2 patients presenting with hearing and vision loss, and the Dent disease (DD) classical renal phenotype, that is, low molecular weight proteinuria (LMWP), hypercalciuria and nephrocalcinosis/nephrolithiasis. We propose that a subset of patients presenting as DD may represent unrecognized cases or mild forms of Donnai-Barrow/facio-oculo-acustico-renal (DB/FOAR) syndrome or be on the phenotypic continuum between the 2 conditions. PMID: 29532936 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - March 13, 2018 Category: Genetics & Stem Cells Authors: Anglani F, Terrin L, Brugnara M, Battista M, Cantaluppi V, Ceol M, Bertoldi L, Valle G, Joy MP, Pober BR, Longoni M Tags: Clin Genet Source Type: research

Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.
Abstract Distinguishing autosomal dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cy...
Source: Clinical Genetics - March 9, 2018 Category: Genetics & Stem Cells Authors: Fujimaru T, Mori T, Sekine A, Mandai S, Chiga M, Kikuchi H, Ando F, Mori Y, Nomura N, Iimori S, Naito S, Okado T, Rai T, Hoshino J, Ubara Y, Uchida S, Sohara E Tags: Clin Genet Source Type: research

The D313Y genotype-Pathogenic mutation or polymorphism?
PMID: 29521444 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - March 9, 2018 Category: Genetics & Stem Cells Authors: Oder D, Wanner C, Nordbeck P Tags: Clin Genet Source Type: research

EFNB2 haploinsufficiency causes a syndromic neurodevelopmental disorder.
We report a patient with a de novo variant in EFNB2 and a family in which segregates a 610-kb deletion at chromosome 13q33 encompassing only ARGLU1 and EFNB2 genes. The de novo variant was observed in a patient with anal stenosis, hypoplastic left ventricle and mild developmental delay. The deletion was identified in 2 sibs with congenital heart defect and mild developmental delay. One of the affected sibs further had myoclonic epilepsy and bilateral sensorineural hearing loss. The carrier mother was apparently asymptomatic. Because EFNB2 is located in the subtelomeric region of 13q chromosome, we reviewed the previous rep...
Source: Clinical Genetics - March 6, 2018 Category: Genetics & Stem Cells Authors: Lévy J, Haye D, Marziliano N, Casu G, Guimiot F, Dupont C, Teissier N, Benzacken B, Gressens P, Pipiras E, Verloes A, Tabet AC Tags: Clin Genet Source Type: research

Unexpected diagnosis of a SHH nonsense variant causing a variable phenotype ranging from familial coloboma and Intellectual disability to isolated microcephaly.
net C PMID: 29498412 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - March 2, 2018 Category: Genetics & Stem Cells Authors: Bruel AL, Thevenon J, Huet F, Jean-Marcais N, Odent S, Dubourg C, Lehalle D, Tran Mau-Them F, Philippe C, Moutton S, Houcinat N, Gay S, Guibaud L, Duffourd Y, Rivière JB, Faivre L, Thauvin-Robinet C Tags: Clin Genet Source Type: research

Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma.
Abstract Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting i...
Source: Clinical Genetics - March 2, 2018 Category: Genetics & Stem Cells Authors: Scholz C, Golas MM, Weber RG, Hartmann C, Lehmann U, Sahm F, Schmidt G, Auber B, Sturm M, Schlegelberger B, Illig T, Steinemann D, Hofmann W Tags: Clin Genet Source Type: research

ZNF687 mutations are frequently found in pagetic patients from South Italy: implication in the pathogenesis of Paget's disease of bone.
Abstract Paget's disease of bone (PDB) is a skeletal disorder whose molecular basis are not fully elucidated. However, 10% of patients show a familial PDB and 35% of them carry mutations in the SQSTM1 gene. We recently reported a founder mutation (p.Pro937Arg) in the ZNF687 gene, underlying PDB complicated by Giant Cell Tumor (GCT/PDB) and rarely occurring in PDB patients without neoplastic degeneration. Since 80% of Italian GCT/PDB patients derive from Avellino, we hypothesized that ZNF687 mutation rate was higher in this region than elsewhere. Interestingly, our molecular analysis on 30 PDB patients showed that ...
Source: Clinical Genetics - March 1, 2018 Category: Genetics & Stem Cells Authors: Divisato G, di Carlo FS, Petrillo N, Esposito T, Gianfrancesco F Tags: Clin Genet Source Type: research

2p24.2 (rs7552) is a susceptibility locus for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.
ta RD Abstract The population of Brazil is highly admixed, with each individual showing variable levels of Amerindian, European and African ancestry, which may interfere in the genetic susceptibility of known risk loci to nonsyndromic cleft lip with or without cleft palate (NSCL±P). Here we investigated 5 reported genome-wide loci for NSCL±P in an ancestry-structured case-control study containing 1,697 Brazilian participants (831 NSCL±P and 866 healthy controls). SNPs rs7552 in 2q24.2, rs8049367 in 16p13.3, rs1880646, rs7406226, rs9891446 in 17p13, rs1588366 in 17q23.2 and rs73039426 in 19q13....
Source: Clinical Genetics - February 28, 2018 Category: Genetics & Stem Cells Authors: Machado RA, Nogueira EN, Martelli-Júnior H, Reis SR, Persuhn DC, Coletta RD Tags: Clin Genet Source Type: research

Regulatory network analysis of LINC00472, a long noncoding RNA downregulated by DNA hypermethylation in colorectal cancer.
Abstract Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein-coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC-associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues...
Source: Clinical Genetics - February 28, 2018 Category: Genetics & Stem Cells Authors: Chen L, Zhang W, Li DY, Wang X, Tao Y, Zhang Y, Dong C, Zhao J, Zhang L, Zhang X, Guo J, Zhang X, Liao Q Tags: Clin Genet Source Type: research

CKAP2L mutation confirms the diagnosis of Filippi syndrome.
o S PMID: 29473684 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - February 23, 2018 Category: Genetics & Stem Cells Authors: Capecchi G, Baldassarri M, Ferranti S, Guidoni E, Cioni M, Nürnberg P, Mencarelli MA, Renieri A, Grosso S Tags: Clin Genet Source Type: research

Molecular and clinical studies in eight patients with Temple syndrome.
Abstract Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by phenotypic features including pre- and postnatal growth retardation, muscular hypotonia and feeding difficulties in infancy, early puberty and short stature with small hands and feet and often truncal obesity. It is caused by maternal uniparental disomies, paternal deletions and primary imprinting defects that affect the chromosomal region 14q32 and lead to a disturbed expression of imprinted genes in this region. Here we present detailed clinical data of eight patients with Temple syndrome, four with an imprinting defect, two ...
Source: Clinical Genetics - February 22, 2018 Category: Genetics & Stem Cells Authors: Gillessen-Kaesbach G, Albrecht B, Eggermann T, Elbracht M, Mitter D, Morlot S, van Ravenswaaij-Arts CMA, Schulz S, Strobl-Wildemann G, Buiting K, Beygo J Tags: Clin Genet Source Type: research

Truncating variants of the DLG4 gene are responsible for intellectual disability with marfanoid features.
el TR, Laurence F Abstract Marfanoid habitus (MH) combined with intellectual disability (ID) is a genetically and clinically heterogeneous group of overlapping disorders. We performed exome sequencing in 33 trios and 31 single probands to identify novel genes specific to MH-ID. After the search for variants in OMIM genes and non-OMIM genes with classical approaches, we searched for variants in non-disease-causing genes whose pLI was above 0.9 (ExAC Consortium data), in which truncating variants were found in at least 3 unrelated patients, in order to identity novel MH-ID genes. Only DLG4 gene met these criteria. D...
Source: Clinical Genetics - February 20, 2018 Category: Genetics & Stem Cells Authors: Sébastien M, Ange-Line B, Mirna A, Martin C, Elisabeth S, Cyril G, Anne-Marie G, Aude C, Perrine C, Delphine H, Anne F, Nada H, Antonio V, Frédéric TM, Christophe P, Yannis D, Christel TR, Laurence F Tags: Clin Genet Source Type: research

Expanding the histopathological spectrum of CFL2-related myopathies.
Abstract Congenital myopathies (CMs) caused by mutation in cofilin-2 gene (CFL2) show phenotypic heterogeneity ranging from early onset and rapid progressive forms to milder myopathy. Muscle histology is also heterogeneous showing rods and /or myofibrillar changes. Here, we report on three new cases, from two unrelated families, of severe CM related to novel homozygous or compound heterozygous loss-of-function mutations in CFL2. Peculiar histopathological changes showed nemaline bodies and thin filaments accumulations together to myofibrillar changes, which were evocative of the muscle findings observed in Cfl2-/-...
Source: Clinical Genetics - February 19, 2018 Category: Genetics & Stem Cells Authors: Fattori F, Fiorillo C, Rodolico C, Tasca G, Verardo M, Bellacchio E, Pizzi S, Ciolfi A, Fagiolari G, Lupica A, Broda P, Pedemonte M, Moggio M, Bruno C, Tartaglia M, Bertini E, D'Amico A Tags: Clin Genet Source Type: research

Genetic Investigation of 93 Families with Microphthalmia or Posterior Microphthalmos.
Majid S, Aldahmesh MA, Alkuraya FS Abstract Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing (WES) and mole...
Source: Clinical Genetics - February 16, 2018 Category: Genetics & Stem Cells Authors: Patel N, Khan AO, Alsahli S, Abdel-Salam G, Nowilaty SR, Mansour AM, Nabil A, Al-Owain M, Sogati S, Salih MA, Kamal AM, Alsharif H, Alsaif H, Alzahrani SS, Abdulwahab F, Ibrahim N, Hashem M, Faquih T, Shah ZA, Abouelhoda M, Monies D, Dasouki M, Shaheen R, Tags: Clin Genet Source Type: research

INTU-related oral-facial-digital syndrome type VI: a confirmatory report.
This report of a second patient with INTU-related OFD and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD to be classified within the OFD VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect. PMID: 29451301 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - February 16, 2018 Category: Genetics & Stem Cells Authors: Bruel AL, Levy J, Elenga N, Defo A, Favre A, Lucron H, Capri Y, Perrin L, Passemard S, Vial Y, Tabet AC, Faivre L, Thauvin-Robinet C, Verloes A Tags: Clin Genet Source Type: research

A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the ER quality control in the mechanism of some β3GalT6-pathy mutations.
We report a disease-causing variant c.618C>G, p.(Cys206Trp) in one patient originally described as Al-Gazali syndrome and reported in 1999. We evaluated the involvement of the Endoplasmic-reticulum-associated protein degradation (ERAD), in the pathogenesis of thirteen B3GALT6 variants. Retention in ER was evident in six of them while the c.618C>G, p.(Cys206Trp) and the other six variants trafficked normally. Our findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome and suggest that Al-Gazali syndrome represents the severe end of the spectrum of the phenotypes caused by pathogenic varia...
Source: Clinical Genetics - February 14, 2018 Category: Genetics & Stem Cells Authors: Ben-Mahmoud A, Ben-Salem S, Al-Sorkhy M, John A, Ali BR, Al-Gazali L Tags: Clin Genet Source Type: research

Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability.
We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in two female siblings with three homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinic...
Source: Clinical Genetics - February 13, 2018 Category: Genetics & Stem Cells Authors: Rangel-Sosa MM, Figuera-Villanueva LE, González-Ramos IA, Pérez-Páramo YX, Martínez-Jacobo LA, Arnaud-López L, Nastasi-Catanese JA, Rivas-Estilla AM, Galán-Huerta KA, Rojas-Martínez A, Ortiz-López R, Córdova-Fletes C Tags: Clin Genet Source Type: research

Cancer gene-panel testing identifies two loss-of-function alleles in PALB2 and PTEN.
Abstract Synchronous loss-of-function mutations in the cancer predisposing genes, PTEN and PALB2 identified by multigene panel. PMID: 29430632 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - February 11, 2018 Category: Genetics & Stem Cells Authors: Avgerinou C, Fostira F, Economopoulou P, Psyrri A Tags: Clin Genet Source Type: research

Characteristics of genetic diseases in consanguineous populations in the genomic era: lessons from Arab communities in North Israel.
Abstract The health outcome of consanguineous/endogamous unions is an increased risk of autosomal recessive disorders in their progeny. This manuscript is focused on consanguineous/endogamous populations living in North Israel. Molecular tools show that spouses' relatedness and hence their risks for congenital diseases among offspring are often greater than the risk calculated on the basis of reported pedigrees. Revealing founder mutations allows for effective genetic counseling, but also induces genetic screening of the whole community in case the mutations are found to be frequent. More complex genetic mechanism...
Source: Clinical Genetics - February 10, 2018 Category: Genetics & Stem Cells Authors: Shalev SA Tags: Clin Genet Source Type: research

Intrafamiliar clinical variability of Circumferential Skin Creases Kunze Type caused by a novel heterozygous mutation of N-terminal TUBB gene.
We report a 9-year-old boy with a diagnosis of CSC-KT based on MTBS, facial dysmorphism, microcephaly, severe ID, cortical atrophy and corpus callosum hypoplasia. Sanger sequencing identified a novel heterozygous c.218T>C (p.Met73Thr) mutation in the N-terminal of TUBB gene, that was inherited from the mother affected by isolated MTBS. This is the first report of inherited TUBB gene-related CSC-KT resulting from a novel heterozygous mutation in the N-terminal domain. Present data support the role of TUBB mutations in CSC-KT and definitely includes CSC-KT syndrome within the tubulinopathies. PMID: 29427453 [PubMed -...
Source: Clinical Genetics - February 10, 2018 Category: Genetics & Stem Cells Authors: Dentici ML, Terracciano A, Bellacchio E, Capolino R, Novelli A, Digilio MC, Dallapiccola B Tags: Clin Genet Source Type: research

Identification of a novel lethal form of autosomal recessive ichthyosis caused by UDP-glucose ceramide glucosyltransferase deficiency.
PMID: 29417556 [PubMed - as supplied by publisher] (Source: Clinical Genetics)
Source: Clinical Genetics - February 8, 2018 Category: Genetics & Stem Cells Authors: Monies D, Anabrees J, Ibrahim N, Elbardisy H, Abouelhoda M, Meyer BF, Alkuraya FS Tags: Clin Genet Source Type: research

Rare, genetically conditioned forms of rickets - differential diagnosis and advances in diagnostics and treatment.
Abstract Apart from the classic forms of rickets, there are rare genetic disorders from the group of vitamin D-resistant rickets where the clinical picture is very similar to the classic forms. Diagnosis of genetically conditioned rickets is often delayed. It is very important to know that a disorder of genetic background may be the cause of the failure of classic treatment in patients with rachitic symptoms. In the group of genetically conditioned rickets there are, among others, congenital hypophosphatemic rickets and vitamin D-dependent rickets type I and II. Congenital hypophosphatemic rickets is characterised...
Source: Clinical Genetics - February 8, 2018 Category: Genetics & Stem Cells Authors: Michałus I, Rusińska A Tags: Clin Genet Source Type: research

Genetic and Clinical Findings in a Chinese Cohort of Patients with collagen VI-Related Myopathies.
Abstract Collagen VI-related myopathy, caused by pathogenic variants in the genes encoding collagen VI, represents a clinical continuum from Ullrich congenital muscular dystrophy (UCMD) to Bethlem myopathy (BM). Clinical data of 60 probands and their family members were collected and muscle biopsies of 26 patients were analyzed. COL6A1, COL6A2 and COL6A3 exons were analyzed by direct sequencing or next generation sequencing (NGS). Sixty patients were characterized by delayed motor milestones, muscle weakness, skin and joint changes with forty UCMD and twenty BM. Muscle with biopsies revealed dystrophic changes and...
Source: Clinical Genetics - February 8, 2018 Category: Genetics & Stem Cells Authors: Fan Y, Liu A, Wei C, Yang H, Chang X, Wang S, Yuan Y, Bonnemann C, Wu Q, Wu X, Xiong H Tags: Clin Genet Source Type: research