abstract：:The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using informat...

journal_title：Human mutation

authors： Felicio PS,Grasel RS,Campacci N,de Paula AE,Galvão HCR,Torrezan GT,Sabato CS,Fernandes GC,Souza CP,Michelli RD,Andrade CE,Barros BDF,Matsushita MM,Revil T,Ragoussis J,Couch FJ,Hart SN,Reis RM,Melendez ME,Tonin PN,

更新日期：2020-12-16 00:00:00

abstract：:There is a well-recognized growing need for improved access to online genetic and genomics education for professionals, students, teachers, and the public. Numerous individual online genetic and genomic educational resources have been developed, but many are difficult to identify or locate when required. Consequently,...

journal_title：Human mutation

authors： Tobias AP,Tobias ES

更新日期：2020-12-01 00:00:00

abstract：:Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-...

journal_title：Human mutation

authors： García-Recio A,Santos-Gómez A,Soto D,Julia-Palacios N,García-Cazorla À,Altafaj X,Olivella M

更新日期：2020-11-30 00:00:00

abstract：:Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homo...

journal_title：Human mutation

authors： Hu TY,Zhang H,Meng LL,Yuan SM,Tu CF,Du J,Lu GX,Lin G,Nie HC,Tan YQ

更新日期：2020-11-10 00:00:00

abstract：:Alpha-chain collagen molecules encoded by genes that include COL11A1 are essential for skeletal, ocular, and auditory function. COL11A1 variants have been reported in syndromes involving these organ systems. However, a description of the complete clinical spectrum is lacking, as evidenced by a recent association of au...

journal_title：Human mutation

authors： Rad A,Schade-Mann T,Gamerdinger P,Yanus GA,Schulte B,Müller M,Imyanitov EN,Biskup S,Löwenheim H,Tropitzsch A,Vona B

更新日期：2020-11-10 00:00:00

abstract：:The penetrance of the p.[Met694Val];[Met694Val] genotype of pyrin in adult familial Mediterranean fever (FMF) patients is close to 100%. Disease penetrance of the p.[Met694Val];[Glu148Gln] genotype (M694V/E148Q), and the heterozygous p.[Met694Val];[=] genotype is unknown. A difference in the penetrance of the latter t...

journal_title：Human mutation

authors： Eyal O,Shinar Y,Pras M,Pras E

更新日期：2020-11-01 00:00:00

abstract：:Stargardt macular degeneration (Stargardt disease 1 [STGD1]) is caused by mutations in the gene encoding ABCA4, an ATP-binding cassette protein that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across photoreceptor membranes. Reduced ABCA4 activity results in retinoid accumulation leading to photorece...

journal_title：Human mutation

authors： Curtis SB,Molday LL,Garces FA,Molday RS

更新日期：2020-11-01 00:00:00

abstract：:Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-gen...

journal_title：Human mutation

authors： Pettersson M,Grochowski CM,Wincent J,Eisfeldt J,Breman AM,Cheung SW,Krepischi ACV,Rosenberg C,Lupski JR,Ottosson J,Lovmar L,Gacic J,Lundberg ES,Nilsson D,Carvalho CMB,Lindstrand A

更新日期：2020-11-01 00:00:00

abstract：:Recessively inherited limb girdle muscular dystrophy (LGMD) type 2A is the most common LGMD worldwide. Here, we report the first single missense variant in CAPN3 causing dominantly inherited calpainopathy. A 43-year-old proband, his father and two sons were heterozygous for a c.1715G>C p.(Arg572Pro) variant in CAPN3. ...

journal_title：Human mutation

authors： Vissing J,Dahlqvist JR,Roudaut C,Poupiot J,Richard I,Duno M,Krag T

更新日期：2020-09-01 00:00:00

abstract：:PITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a "lower limb" appearance; PITX1 deletions or missense variation cause a...

journal_title：Human mutation

authors： Morel G,Duhamel C,Boussion S,Frénois F,Lesca G,Chatron N,Labalme A,Sanlaville D,Edery P,Thevenon J,Faivre L,Fassier A,Prodhomme O,Escande F,Manouvrier S,Petit F,Geneviève D,Rossi M

更新日期：2020-09-01 00:00:00

abstract：:Recently, we demonstrated that the qualitative American College of Medical Genetics and Genomics/Association for Medical Pathology (ACMG/AMP) guidelines for evaluation of Mendelian disease gene variants are fundamentally compatible with a quantitative Bayesian formulation. Here, we show that the underlying ACMG/AMP "s...

journal_title：Human mutation

authors： Tavtigian SV,Harrison SM,Boucher KM,Biesecker LG

更新日期：2020-07-27 00:00:00

abstract：:Int22h1/Int22h2-mediated Xq28 duplication syndrome is a relatively new X-linked intellectual disability syndrome, arising from duplications of the subregion flanked by intron 22 homologous regions 1 and 2 on the q arm of chromosome X. Its primary manifestations include variable cognitive deficits, distinct facial dysm...

journal_title：Human mutation

authors： Ballout RA,Dickerson C,Wick MJ,Al-Sweel N,Openshaw AS,Srivastava S,Swanson LC,Bramswig NC,Kuechler A,Hong B,Fleming LR,Curry K,Robertson SP,Andersen EF,El-Hattab AW

更新日期：2020-07-01 00:00:00

abstract：:CACNA1H genetic variants were originally reported in a childhood absence epilepsy cohort. Subsequently, genetic testing for CACNA1H became available and is currently offered by commercial laboratories. However, the current status of CACNA1H as a monogenic cause of epilepsy is controversial, highlighted by ClinGen's re...

journal_title：Human mutation

authors： Calhoun JD,Huffman AM,Bellinski I,Kinsley L,Bachman E,Gerard E,Kearney JA,Carvill GL

更新日期：2020-06-01 00:00:00

abstract：:MUSK encodes the muscle-specific receptor tyrosine kinase (MuSK), a key component of the agrin-LRP4-MuSK-DOK7 signaling pathway, which is essential for the formation and maintenance of highly specialized synapses between motor neurons and muscle fibers. We report a patient with severe early-onset congenital myasthenic...

journal_title：Human mutation

authors： Rodríguez Cruz PM,Cossins J,Cheung J,Maxwell S,Jayawant S,Herbst R,Waithe D,Kornev AP,Palace J,Beeson D

更新日期：2020-03-01 00:00:00

abstract：:The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants fr...

journal_title：Human mutation

authors： Gao X,Nan X,Liu Y,Liu R,Zang W,Shan G,Gai F,Zhang J,Li L,Cheng G,Song L

更新日期：2020-03-01 00:00:00

abstract：:Pathogenic GFM1 variants have been linked to neurological phenotypes with or without liver involvement, but only a few cases have been reported in the literature. Here, we report clinical, biochemical, and neuroimaging findings from nine unrelated children carrying GFM1 variants, 10 of which were not previously report...

journal_title：Human mutation

authors： Barcia G,Rio M,Assouline Z,Zangarelli C,Gueguen N,Dumas VD,Marcorelles P,Schiff M,Slama A,Barth M,Hully M,de Lonlay P,Munnich A,Desguerre I,Bonnefont JP,Steffann J,Procaccio V,Boddaert N,Rötig A,Metodiev MD,Ruzzen

更新日期：2020-02-01 00:00:00

abstract：:Fumarate hydratase (FH) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring ...

journal_title：Human mutation

authors： Zhang L,Walsh MF,Jairam S,Mandelker D,Zhong Y,Kemel Y,Chen YB,Musheyev D,Zehir A,Jayakumaran G,Brzostowski E,Birsoy O,Yang C,Li Y,Somar J,DeLair D,Pradhan N,Berger MF,Cadoo K,Carlo MI,Robson ME,Stadler ZK,Iaco

更新日期：2020-01-01 00:00:00

abstract：:Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the α subunit of the delayed rectifier voltage-dependent potassium channel Kv 2.1. We review the 3...

journal_title：Human mutation

authors： Bar C,Barcia G,Jennesson M,Le Guyader G,Schneider A,Mignot C,Lesca G,Breuillard D,Montomoli M,Keren B,Doummar D,Billette de Villemeur T,Afenjar A,Marey I,Gerard M,Isnard H,Poisson A,Dupont S,Berquin P,Meyer P,Gene

更新日期：2020-01-01 00:00:00

abstract：:Xq22 deletions that encompass PLP1 (Xq22-PLP1-DEL) are notable for variable expressivity of neurological disease traits in females ranging from a mild late-onset form of spastic paraplegia type 2 (MIM# 312920), sometimes associated with skewed X-inactivation, to an early-onset neurological disease trait (EONDT) of sev...

journal_title：Human mutation

authors： Hijazi H,Coelho FS,Gonzaga-Jauregui C,Bernardini L,Mar SS,Manning MA,Hanson-Kahn A,Naidu S,Srivastava S,Lee JA,Jones JR,Friez MJ,Alberico T,Torres B,Fang P,Cheung SW,Song X,Davis-Williams A,Jornlin C,Wight PA,Paty

更新日期：2020-01-01 00:00:00

abstract：:Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of I...

journal_title：Human mutation

authors： Sharon D,Ben-Yosef T,Goldenberg-Cohen N,Pras E,Gradstein L,Soudry S,Mezer E,Zur D,Abbasi AH,Zeitz C,Cremers FPM,Khan MI,Levy J,Rotenstreich Y,Birk OS,Ehrenberg M,Leibu R,Newman H,Shomron N,Banin E,Perlman I

更新日期：2020-01-01 00:00:00

abstract：:Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient-specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well-studied. In advance of human therapeutic...

journal_title：Human mutation

authors： Wert KJ,Koch SF,Velez G,Hsu CW,Mahajan M,Bassuk AG,Tsang SH,Mahajan VB

更新日期：2019-12-01 00:00:00

abstract：:Mutations in the human voltage-gated K+ channel subunit KV 4.3-encoding KCND3 gene have been associated with the autosomal dominant neurodegenerative disorder spinocerebellar ataxia types 19 and 22 (SCA19/22). The precise pathophysiology underlying the dominant inheritance pattern of SCA19/22 remains elusive. Using ce...

journal_title：Human mutation

authors： Hsiao CT,Fu SJ,Liu YT,Lu YH,Zhong CY,Tang CY,Soong BW,Jeng CJ

更新日期：2019-11-01 00:00:00

abstract：:Noncoding RNAs have been widely recognized as essential mediators of gene regulation. However, in contrast to protein-coding genes, much less is known about the influence of noncoding RNAs on human diseases. Here we examined the association of genetic variants located in primary microRNA sequences and long noncoding R...

journal_title：Human mutation

authors： Ghanbari M,Munshi ST,Ma B,Lendemeijer B,Bansal S,Adams HH,Wang W,Goth K,Slump DE,van den Hout MCGN,van IJcken WFJ,Bellusci S,Pan Q,Erkeland SJ,de Vrij FMS,Kushner SA,Ikram MA

更新日期：2019-11-01 00:00:00

abstract：:Familial cerebral cavernous malformation (FCCM) is an autosomal dominant vascular disorder caused by heterozygous deleterious variants in KRIT1, CCM2 or PDCD10. In a previous study, we presented the clinical and molecular findings in 140 FCCM individuals. In the present work, we report supporting information on (a) ap...

journal_title：Human mutation

authors： Fusco C,Copetti M,Mazza T,Amoruso L,Mastroianno S,Nardella G,Guarnieri V,Micale L,D'Agruma L,Castori M

更新日期：2019-11-01 00:00:00

abstract：:A subset of a larger and heterogeneous class of disorders, the congenital myasthenic syndromes (CMS) are caused by pathogenic variants in genes encoding proteins that support the integrity and function of the neuromuscular junction (NMJ). A central component of the NMJ is the sodium-dependent high-affinity choline tra...

journal_title：Human mutation

authors： Banerjee M,Arutyunov D,Brandwein D,Janetzki-Flatt C,Kolski H,Hume S,Leonard NJ,Watt J,Lacson A,Baradi M,Leslie EM,Cordat E,Caluseriu O

更新日期：2019-10-01 00:00:00

abstract：:Genome sequencing identifies vast number of genetic variants. Predicting these variants' molecular and clinical effects is one of the preeminent challenges in human genetics. Accurate prediction of the impact of genetic variants improves our understanding of how genetic information is conveyed to molecular and cellula...

journal_title：Human mutation

authors： Hu Z,Yu C,Furutsuki M,Andreoletti G,Ly M,Hoskins R,Adhikari AN,Brenner SE

更新日期：2019-09-01 00:00:00

abstract：:With the advent of rapid sequencing technologies, making sense of all the genomic variations that we see among us has been a major challenge. A plethora of algorithms and methods exist that try to address genome interpretation through genotype-phenotype linkage analysis or evaluating the loss of function/stability mut...

journal_title：Human mutation

authors： Garg A,Pal D

更新日期：2019-09-01 00:00:00

abstract：:The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies in NAGLU ac...

journal_title：Human mutation

authors： Clark WT,Kasak L,Bakolitsa C,Hu Z,Andreoletti G,Babbi G,Bromberg Y,Casadio R,Dunbrack R,Folkman L,Ford CT,Jones D,Katsonis P,Kundu K,Lichtarge O,Martelli PL,Mooney SD,Nodzak C,Pal LR,Radivojac P,Savojardo C,Shi

更新日期：2019-09-01 00:00:00

abstract：:Here we present a computational model, Score of Unified Regulatory Features (SURF), that predicts functional variants in enhancer and promoter elements. SURF is trained on data from massively parallel reporter assays and predicts the effect of variants on reporter expression levels. It achieved the top performance in ...

journal_title：Human mutation

authors： Dong S,Boyle AP

更新日期：2019-09-01 00:00:00

abstract：:The CAGI-5 pericentriolar material 1 (PCM1) challenge aimed to predict the effect of 38 transgenic human missense mutations in the PCM1 protein implicated in schizophrenia. Participants were provided with 16 benign variants (negative controls), 10 hypomorphic, and 12 loss of function variants. Six groups participated ...

journal_title：Human mutation

authors： Monzon AM,Carraro M,Chiricosta L,Reggiani F,Han J,Ozturk K,Wang Y,Miller M,Bromberg Y,Capriotti E,Savojardo C,Babbi G,Martelli PL,Casadio R,Katsonis P,Lichtarge O,Carter H,Kousi M,Katsanis N,Andreoletti G,Moult J

更新日期：2019-09-01 00:00:00

abstract：:Pathogenic genetic variants often primarily affect splicing. However, it remains difficult to quantitatively predict whether and how genetic variants affect splicing. In 2018, the fifth edition of the Critical Assessment of Genome Interpretation proposed two splicing prediction challenges based on experimental perturb...

journal_title：Human mutation

authors： Cheng J,Çelik MH,Nguyen TYD,Avsec Ž,Gagneur J

更新日期：2019-09-01 00:00:00

abstract：:Increasing use of next-generation sequencing technologies in clinical diagnostics allows large-scale discovery of genetic variants, but also results in frequent identification of variants of unknown significance (VUSs). Their classification into disease-causing and neutral variants is often hampered by the absence of ...

journal_title：Human mutation

authors： Wu H,Vonk KKD,van der Maarel SM,Santen GWE,Daxinger L

更新日期：2019-08-01 00:00:00

abstract：:Human transforming growth factor β-induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progr...

journal_title：Human mutation

authors： Kheir V,Cortés-González V,Zenteno JC,Schorderet DF

更新日期：2019-06-01 00:00:00

abstract：:Syndromic sensorineural hearing loss is multigenic and associated with malformations of the ear and other organ systems. Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation. Next-g...

journal_title：Human mutation

authors： Macnamara EF,Koehler AE,D'Souza P,Estwick T,Lee P,Vezina G,Undiagnosed Diseases Network.,Fauni H,Braddock SR,Torti E,Holt JM,Sharma P,Malicdan MCV,Tifft CJ

更新日期：2019-05-01 00:00:00

abstract：:Though many mutations have been identified to be associated with the occurrence of congenital cataract, pathogenic loci in some affected families are still unknown. Clinical data and genomic DNA were collected from a four-generation Chinese family. Candidate mutations were independently verified for cosegregation in t...

journal_title：Human mutation

authors： Sun M,Chen C,Hou S,Li X,Wang H,Zhou J,Chen X,Liu P,Kijlstra A,Lin S,Ye J

更新日期：2019-04-01 00:00:00

abstract：:Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causati...

journal_title：Human mutation

authors： Guo XX,Zou XH,Wang C,Yao XP,Su HZ,Lai LL,Chen HT,Lai JH,Liu YB,Chen DP,Deng YC,Lin P,Lin HS,Hong BC,Yao QY,Chen XJ,Huang DQ,Fu HX,Peng JD,Niu YF,Zhao YY,Zhu XQ,Lu XP,Lin HL,Li YK,Liu CY,Huang GB,Wang

更新日期：2019-04-01 00:00:00

abstract：:The PCDH19 gene consists of six exons encoding a 1,148 amino acid transmembrane protein, Protocadherin 19, which is involved in brain development. Heterozygous pathogenic variants in this gene are inherited in an unusual X-linked dominant pattern in which heterozygous females are affected, while hemizygous males are t...

journal_title：Human mutation

authors： Niazi R,Fanning EA,Depienne C,Sarmady M,Abou Tayoun AN

更新日期：2019-03-01 00:00:00

abstract：:Both genetic and epigenetic abnormalities play important roles in gastric cancer (GC) development. We investigated whether the molecular subtypes of gastric cancer by combining genetic and epigenetic anomalies define its clinicopathological features and prognosis. The CpG island methylator phenotype (CIMP), MLH1 methy...

journal_title：Human mutation

authors： Tahara T,Tahara S,Horiguchi N,Okubo M,Terada T,Yamada H,Yoshida D,Omori T,Osaki H,Maeda K,Kamano T,Funasaka K,Nagasaka M,Nakagawa Y,Shibata T,Ohmiya N

更新日期：2019-03-01 00:00:00

abstract：:Several recent reports have described a missense variant in the gene NR5A1 (c.274C>T; p.Arg92Trp) in a significant number of 46,XX ovotesticular or testicular disorders of sex development (DSDs) cases. The affected residue falls within the DNA-binding domain of the NR5A1 protein, however the exact mechanism by which i...

journal_title：Human mutation

authors： Knarston IM,Robevska G,van den Bergen JA,Eggers S,Croft B,Yates J,Hersmus R,Looijenga LHJ,Cameron FJ,Monhike K,Ayers KL,Sinclair AH

更新日期：2019-02-01 00:00:00

abstract：:Homocystinuria is a rare inborn error of methionine metabolism caused by cystathionine β-synthase (CBS) deficiency. The prevalence of homocystinuria in Qatar is 1:1,800 births, mainly due to a founder Qatari missense mutation, c.1006C>T; p.R336C (p.Arg336Cys). We characterized the structure-function relationship of th...

journal_title：Human mutation

authors： Ismail HM,Krishnamoorthy N,Al-Dewik N,Zayed H,Mohamed NA,Giacomo VD,Gupta S,Häberle J,Thöny B,Blom HJ,Kruger WD,Ben-Omran T,Nasrallah GK

更新日期：2019-02-01 00:00:00