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1.
Field M Scheffer IE Gill D Wilson M Christie L Shaw M Gardner A Glubb G Hobson L Corbett M Friend K Willis-Owen S Gecz J 《European journal of human genetics : EJHG》2012,20(7):806-809
Using a combination of linkage mapping and massively parallel sequencing of the X-chromosome exome, we identified an 18-bp deletion in exon 8 of the oral-facial-digital syndrome type 1 (OFD1) gene in a family with X-linked Joubert syndrome (JBTS10). The deletion results in an in-frame deletion of six amino acids. New features not noted in the two previously reported cases of X-linked Joubert syndrome include the presence of polycystic kidney disease, polymicrogyria and hydrocephalus. Our study further underlines the power of genetic mapping combined with massively parallel sequencing as a powerful tool for novel disease gene and mutation discovery. 相似文献
2.
Alyssa L. Ritter Jessica Gold Hiroshi Hayashi Amanda M. Ackermann Stephanie Hanke Cara Skraban Sanmati Cuddapah Elizabeth Bhoj Dong Li Yukiko Kuroda Jessica Wen Ryojun Takeda Audrey Bibb Salima El Chehadeh Amélie Piton Jeanine Ohl Mary K. Kukolich Keisuke Nagasaki Kosuke Izumi 《Genetics in medicine》2022,24(6):1227-1237
PurposeThis study aimed to describe the phenotypic and molecular characteristics of ARCN1-related syndrome.MethodsPatients with ARCN1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient.ResultsIn total, we identified 14 cases of ARCN1-related syndrome, (9 pediatrics, and 5 fetal cases from 3 families). The clinical features these newly identified cases were compared to 6 previously reported cases for a total of 20 cases. Intrauterine growth restriction, micrognathia, and short stature were present in all patients. Other common features included prematurity (11/15, 73.3%), developmental delay (10/14, 71.4%), genitourinary malformations in males (6/8, 75%), and microcephaly (12/15, 80%). Novel features of ARCN1-related syndrome included transient liver dysfunction and specific glycosylation abnormalities during illness, giant cell hepatitis, hepatoblastoma, cataracts, and lethal skeletal manifestations. Developmental delay was seen in 73% of patients, but only 3 patients had intellectual disability, which is less common than previously reported.ConclusionARCN1-related syndrome presents with a wide clinical spectrum ranging from a severe embryonic lethal syndrome to a mild syndrome with intrauterine growth restriction, micrognathia, and short stature without intellectual disability. Patients with ARCN1-related syndrome should be monitored for liver dysfunction during illness, cataracts, and hepatoblastoma. Additional research to further define the phenotypic spectrum and possible genotype–phenotype correlations are required. 相似文献
3.
4.
Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences 总被引:1,自引:0,他引:1
Chang EH Menezes M Meyer NC Cucci RA Vervoort VS Schwartz CE Smith RJ 《Human mutation》2004,23(6):582-589
EYA1 mutations cause branchio-oto-renal (BOR) syndrome. These mutations include single nucleotide transitions and transversions, small duplications and deletions, and complex genomic rearrangements. The last cannot be detected by coding sequence analysis of EYA1. We sought to refine the clinical diagnosis of BOR syndrome by analyzing phenotypic data from families segregating EYA1 disease-causing mutations. Based on genotype-phenotype analyses, we propose new criteria for the clinical diagnosis of BOR syndrome. We found that in approximately 40% of persons meeting our criteria, EYA1 mutations were identified. Of these mutations, 80% were coding sequence variants identified by SSCP, and 20% were complex genomic rearrangements identified by a semiquantitative PCR-based screen. We conclude that genetic testing of EYA1 should include analysis of the coding sequence and a screen for complex rearrangements. 相似文献
5.
Shruti Pande Selinda Mascarenhas Aishwarya Venkatraman Vivekananda Bhat Dhanya Lakshmi Narayanan Shahyan Siddiqui Stephanie Bielas Katta Mohan Girisha Anju Shukla 《American journal of medical genetics. Part A》2023,191(8):2175-2180
Heterozygous disease-causing variants in BCL11B are the basis of a rare neurodevelopmental syndrome with craniofacial and immunological involvement. Isolated craniosynostosis, without systemic or immunological findings, has been reported in one of the 17 individuals reported with this disorder till date. We report three additional individuals harboring de novo heterozygous frameshift variants, all lying in the exon 4 of BCL11B. All three individuals presented with the common findings of this disorder i.e. developmental delay, recurrent infections with immunologic abnormalities and facial dysmorphism. Notably, craniosynostosis of variable degree was seen in all three individuals. We, thus add to the evolving genotypes and phenotypes of BCL11B-related BAFopathy and also review the clinical, genomic spectrum along with the underlying disease mechanisms of this disorder. 相似文献
6.
Miguel del Campo Erlane M. Ribeiro Dafne D. G. Horovitz André L. S. Pessoa Giovanny V. A. Fran?a Alfredo García‐Alix Maria J. R. Doriqui Hector Y. C. Wanderley Maria V. T. Sanseverino Jo?o I. C. F. Neri Jo?o M. Pina‐Neto Emerson S. Santos Islane Ver?osa Mirlene C. S. P. Cernach Paula F. V. Medeiros Saile C. Kerbage André A. Silva Vanessa van der Linden Celina M. T. Martelli Marli T. Cordeiro Rafael Dhalia Fernanda S. L. Vianna Cesar G. Victora Lavinia Schuler‐Faccini 《American journal of medical genetics. Part A》2017,173(4):841-857
7.
《European journal of medical genetics》2022,65(1):104377
Carpenter syndrome 1 (CRPT1) is an acrocephalopolysyndactyly (ACPS) disorder characterized by craniosynostosis, polysyndactyly, obesity, and other malformations. It is caused by mutations in the gene RAB23. We are reporting on two patients from two unrelated consanguineous Egyptian families. Patient 1 presented with an atypical clinical presentation of Carpenter syndrome including overgrowth with advanced bone age, epileptogenic changes on electroencephalogram and autistic features. Patient 2 presented with typical clinical features suggestive of Carpenter syndrome. Therefore, Patient 1 was subjected to whole exome sequencing (WES) to find an explanation for his unusual features and Patient 2 was subjected to Sanger sequencing of the coding exons of theRAB23 gene to confirm the diagnosis. We identified a novel homozygous missense RAB23 variant (NM_001278668:c.T416C:p.Leu139Pro) in Patient 1 and a novel homozygous splicing variant (NM_016277.5:c.398+1G > A) in Patient 2. We suggest that the overgrowth with advanced bone age, electroencephalogram epileptogenic changes, and autistic features seen in Patient 1 are an expansion of the Carpenter phenotype and could be due to the novel missense RAB23 variant. Additionally, the novel identified RAB23 variants in Patient 1 and 2 broaden the spectrum of variants associated with Carpenter syndrome. 相似文献
8.
Muroya K Hasegawa T Ito Y Nagai T Isotani H Iwata Y Yamamoto K Fujimoto S Seishu S Fukushima Y Hasegawa Y Ogata T 《Journal of medical genetics》2001,38(6):374-380
We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.
Keywords: GATA3; HDR syndrome; phenotypic spectrum; mutation analysis 相似文献
Keywords: GATA3; HDR syndrome; phenotypic spectrum; mutation analysis 相似文献
9.
《European journal of human genetics : EJHG》2015,23(9):1165-1170
KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed. 相似文献
10.
Expanding the SPECC1L mutation phenotypic spectrum to include Teebi hypertelorism syndrome 下载免费PDF全文
Elizabeth J. Bhoj Dong Li Margaret H. Harr Lifeng Tian Tiancheng Wang Yan Zhao Haijun Qiu Cecilia Kim Jodi D. Hoffman Hakon Hakonarson Elaine H. Zackai 《American journal of medical genetics. Part A》2015,167(11):2497-2502
11.
Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome
Lin DS Chang JH Liu HL Wei CH Yeung CY Ho CS Shu CH Chiang MF Chuang CK Huang YW Wu TY Jian YR Huang ZD Lin SP 《American journal of medical genetics. Part A》2011,(12):3095-3099
De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS. 相似文献
12.
Xin Li Ruen Yao Xin Tan Niu Li Yu Ding Juan Li Guoying Chang Yao Chen Lizhuang Ma Jian Wang Lijun Fu Xiumin Wang 《Clinical genetics》2019,96(4):290-299
Noonan syndrome (NS) is a common autosomal dominant/recessive disorder. No large-scale study has been conducted on NS in China, which is the most populous country in the world. Next-generation sequencing (NGS) was used to identify pathogenic variants in patients that exhibited NS-related phenotypes. We assessed the facial features and clinical manifestations of patients with pathogenic or likely pathogenic variants in the RAS-MAPK signaling pathway. Gene-related Chinese NS facial features were described using artificial intelligence (AI).NGS identified pathogenic variants in 103 Chinese patients in eight NS-related genes: PTPN11 (48.5%), SOS1 (12.6%), SHOC2 (11.7%), KRAS (9.71%), RAF1 (7.77%), RIT1 (6.8%), CBL (0.97%), NRAS (0.97%), and LZTR1 (0.97%). Gene-related facial representations showed that each gene was associated with different facial details. Eight novel pathogenic variants were detected and clinical features because of specific genetic variants were reported, including hearing loss, cancer risk due to a PTPN11 pathogenic variant, and ubiquitous abnormal intracranial structure due to SHOC2 pathogenic variants. NGS facilitates the diagnosis of NS, especially for patients with mild/moderate and atypical symptoms. Our study describes the genotypic and phenotypic spectra of NS in China, providing new insights into distinctive clinical features due to specific pathogenic variants. 相似文献
13.
Yunyun Jiang Michael F. Wangler Amy L. McGuire James R. Lupski Jennifer E. Posey Michael M. Khayat David R. Murdock Luis Sanchez‐Pulido Chris P. Ponting Fan Xia Jill V. Hunter Qingchang Meng Mullai Murugan Richard A. Gibbs 《American journal of medical genetics. Part A》2018,176(6):1315-1326
Xia‐Gibbs syndrome (XGS: OMIM # 615829) results from de novo truncating mutations within the AT‐Hook DNA Binding Motif Containing 1 gene (AHDC1). To further define the phenotypic and molecular spectrum of this disorder, we established an XGS Registry and recruited patients from a worldwide pool of approximately 60 probands. Additional de novo truncating mutations were observed among 25 individuals, extending both the known number of mutation sites and the range of positions within the coding region that were sensitive to alteration. Detailed phenotypic examination of 20 of these patients via clinical records review and data collection from additional surveys showed a wider age range than previously described. Data from developmental milestones showed evidence for delayed speech and that males were more severely affected. Neuroimaging from six available patients showed an associated thinning of the corpus callosum and posterior fossa cysts. An increased risk of both scoliosis and seizures relative to the population burden was also observed. Data from a modified autism screening tool revealed that XGS shares significant overlap with autism spectrum disorders. These details of the phenotypic heterogeneity of XGS implicate specific genotype/phenotype correlations and suggest potential clinical management guidelines. 相似文献
14.
Basel-Vanagaite L Straussberg R Friez MJ Inbar D Korenreich L Shohat M Schwartz CE 《Clinical genetics》2006,69(5):414-419
Mutations in the L1CAM gene cause neurological abnormalities of variable severity, including congenital hydrocephalus, agenesis of the corpus callosum, spastic paraplegia, bilaterally adducted thumbs, aphasia, and mental retardation. Inter- and intrafamilial variability is a well-known feature of the L1CAM spectrum, and several patients have a combination of L1CAM mutations and Hirschsprung's disease (HSCR). We report on two siblings with a missense mutation in exon 7 (p.P240L) of the L1CAM gene. In one of the siblings, congenital dislocation of the radial heads and HSCR were present. Neither patient had hydrocephalus, adducted thumbs, or absent speech, but both had a hypoplastic corpus callosum. We suggest that L1CAM mutation testing should be considered in male patients with a positive family history compatible with X-linked inheritance and either the combination of agenesis of the CC and HSCR or the combination of agenesis of the CC and limb abnormalities, including abnormalities other than adducted thumbs. 相似文献
15.
Monica H. Wojcik Siddharth Srivastava Pankaj B. Agrawal Tugce B. Balci Bert Callewaert Pier Luigi Calvo Diana Carli Michelle Caudle Samantha Colaiacovo Laura Cross Kalliope Demetriou Katy Drazba Marina Dutra-Clarke Matthew Edwards Casie A. Genetti Dorothy K. Grange Scott E. Hickey Bertrand Isidor Sébastien Küry Herbert M. Lachman Alinoe Lavillaureix Michael J. Lyons Carlo Marcelis Elysa J. Marco Julian A. Martinez-Agosto Catherine Nowak Antonio Pizzol Marc Planes Eloise J. Prijoles Evelise Riberi Eric T. Rush Bianca E. Russell Rani Sachdev Betsy Schmalz Deborah Shears David A. Stevenson Kate Wilson Sandra Jansen Bert B. A. de Vries Cynthia J. Curry 《American journal of medical genetics. Part A》2023,191(7):1900-1910
Jansen-de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of PPM1D. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease-causing variants in PPM1D leading to JdVS. Clinical data were provided by treating physicians and/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75 years (range 8 months to 62 years). Four families document autosomal dominant transmission, and 32/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48 months of age. Common manifestations included global developmental delay (35/36, 97%), hypotonia (25/34, 74%), short stature (14/33, 42%), constipation (22/31, 71%), and cyclic vomiting (6/35, 17%). Distinctive personality traits include a hypersocial affect (21/31, 68%) and moderate-to-severe anxiety (18/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in PPM1D with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation. 相似文献
16.
Sarah E. Raible Devanshi Mehta Chiara Bettale Sarah Fiordaliso Maninder Kaur Livija Medne Marlene Rio Eric Haan Susan M. White Kristina Cusmano‐Ozog Eriko Nishi Yiran Guo Honglin Wu Xiaoqing Shi Qingjie Zhao Xueqin Zhang Qi Lei Aimei Lu Xiyu He Nobuhiko Okamoto Noriko Miyake Joseph Piccione Julian Allen Naomichi Matsumoto Mary Pipan Ian D. Krantz Kosuke Izumi 《American journal of medical genetics. Part A》2019,179(7):1126-1138
17.
Tazeen Ashraf Camelia Vaina Dinesh Giri Christine P. Burren Margaret James Amaka C. Offiah Timothy Overton Julia Baptista Sian Ellard Sarah F. Smithson 《American journal of medical genetics. Part A》2020,182(10):2403-2408
Short‐rib polydactyly syndromes are a heterogeneous group of disorders characterized by narrow thorax with short ribs, polydactyly and often other visceral and skeletal malformations. To date there have only been six reported patients with homozygous and compound heterozygous variants in IFT81, causing a short‐rib thoracic dysplasia, with, or without, polydactyly (SRTD19: OMIM 617895). IFT81 is a protein integral to the core of the intraflagellar transport complex B (IFT‐B), which is involved in anterograde transport in the cilium. We describe the case of a male infant with compound heterozygous variants in IFT81, who presented with short long bones, a narrow thorax, polydactyly, and multiple malformations. Three novel clinical features are reported including complete situs inversus, micropenis, and rectal atresia, which have not previously been associated with variants in IFT81. We reviewed the literature and identified the most consistent clinical features associated with this rare ciliopathy syndrome. We postulate that dolichocephaly and sagittal craniosynostosis may be associated with this condition, and provide a clue to considering IFT81 as the causative gene when deciphering complex ciliopathies. 相似文献
18.
Gray MJ Kim CA Bertola DR Arantes PR Stewart H Simpson MA Irving MD Robertson SP 《European journal of human genetics : EJHG》2012,20(1):122-124
Serpentine fibula polycystic kidney syndrome (SFPKS; MIM600330) is a rare skeletal dysplasia that has polycystic kidneys and dysmorphic facies as additional defining phenotypic components. The nosological classification of this disease has been debated as the condition shares features common to other skeletal dysplasias such as Melnick Needles syndrome (MNS; MIM309350) and Hajdu-Cheney Syndrome (HCS; MIM102500). Here, two previously reported cases of SFPKS are presented with emphasis on their phenotypic evolution. With the recent discovery that HCS is caused by mutations in NOTCH2, DNA from the both cases was examined and both were found to have truncating mutations in exon 34 of NOTCH2. The phenotypic evolution of SFPKS and this molecular analysis strongly suggest that SFPKS is part of the phenotypic spectrum of HCS and should no longer be classified as a distinct disease entity. 相似文献
19.
James J. OByrne Maja Tarailo-Graovac Aisha Ghani Michael Champion Charu Deshpande Ali Dursun Riza K. Ozgul Peter Freisinger Ian Garber Tobias B. Haack Rita Horvath Ivo Bari? Ralf A. Husain Leo A.J. Kluijtmans Urania Kotzaeridou Andrew A. Morris Colin J. Ross Saikat Santra Clara D.M. van Karnebeek 《Molecular genetics and metabolism》2018,123(1):28-42