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1.
Smith M Filipek PA Wu C Bocian M Hakim S Modahl C Spence MA 《American journal of medical genetics》2000,96(6):765-770
We have identified a one megabase deletion in the 15q22-15q23 region in a patient with autism, developmental delay, and mild dysmorphism. Genes that map within the deletion region and genes that are interrupted or rearranged at the deletion breakpoints are candidate genes for autism. Fluroescence in situ hybridization studies in this patient revealed that part or all of the PML gene is absent from one chromosome 15 and a BAC clone containing the D15S124 gene locus hybridizes to only one chromosome 15. BAC clones containing the PTPN9, and SLP-1[hUNC24] genes showed markedly reduced hybridization in the 15q22-q23 region on one chromosome 15 in the patient. These BACs also hybridize to the 15q11-q13 region in close proximity to SNRPN and HERC2, and in this region there is equal intensity of signal on the normal and on the deleted chromosome. There are previous reports of deletions and duplications of the 15q11-q13 region in patients with autism. Our patient represents the first report of a 15q22-q23 deletion. Hybridization of the PTPN9 and Slp-1 Bac clones to the 15q11-q13 and the 15q22-q23 regions of chromosome 15 may be due to the presence of PTPN9 or SLP-1 gene sequences or to the presence of other gene sequences or to non-coding homologous DNA sequences. The PTPN9 gene encodes a non-receptor protein tyrosine phosphatase. The Slp-1 [hUNC24] gene is expressed mainly in the brain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:765-770, 2000. 相似文献
2.
Kazuyoshi Fukai Atsushi Kato Satoshi Kimiya Takeo Kubota Richard A. Spritz 《American journal of medical genetics. Part A》2001,104(4):299-302
We describe a woman with 15q11.2–q14 duplication who had clinical manifestations of proximal 15q trisomy and hyperpigmentation. Within this region, the P gene, located at chromosome segment 15q11.2–q12, is associated with oculocutaneous albinism type II (OCA2) and with hypopigmentation in the Prader‐Willi and Angelman chromosome 15q deletion syndromes. We therefore hypothesized that in this woman skin hyperpigmentation might result from a duplication of the P gene. We carried out chromosomal and interphase fluorescence in situ hybridization (I‐FISH) analyses, and determined that the P gene is duplicated in this woman. Our findings demonstrate that trisomy of the P gene can be associated with skin hyperpigmentation. © 2001 Wiley‐Liss, Inc. 相似文献
3.
Janette Moore Michael Daker Sarah Palferman Zoe Docherty 《American journal of medical genetics. Part A》2000,96(1):15-17
A group of 103 subjects with a strict diagnosis of autism were tested for deletion of band q11.2 on the long arm of chromosome 22. No deletions were found, indicating that when a patient has been diagnosed with autism using strict and consistent criteria, in the absence of other indications, it is unlikely that this individual will have a 22q11 deletion. Testing for 22q11 deletions is therefore unlikely to be necessary in these patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:15–17, 2000. © 2000 Wiley‐Liss, Inc. 相似文献
4.
Kyung A Lee Moon Hyang Lee Mark E. Law Syed M. Jalal 《American journal of medical genetics. Part A》2001,104(4):291-294
We describe here a case of a tandem 22/15 translocation with deletion of the 22q13.3–qter region and retention of the NOR of chromosome 15. A 2½‐year‐old Korean girl was referred for chromosome analysis after a clinical evaluation for developmental delay. Physical examination revealed hypotonia, developmental delay, delay of gross motor milestones and speech delay. No dysmorphic features of face, hands or feet were evident in the patient. G‐banded peripheral blood lymphocyte chromosomes showed a tandem translocation between chromosomes 22 and 15, with the satellite stalks of chromosome 15 apparently being retained. All‐telomere FISH analysis using a TTAGGG repeat probe showed absent signals at the junction of the translocation. Sequential G‐banding and FISH analysis using a beta satellite probe showed positive signals close to the junction of the translocation, an indication that the short arms of the chromosome 15 involved in the translocation are retained. FISH with a probe for arylsulfatase, mapped to 22q13.3 region, was negative on the translocation chromosome. Therefore, the 22q13.3 region is deleted. © 2001 Wiley‐Liss, Inc. 相似文献
5.
Yoshie Terada Issei Imoto Hisaki Nagai Kiyotaka Suwa Mariko Momoi Takasi Tajiri Masahiko Onda Johji Inazawa Mitsuru Emi 《American journal of medical genetics. Part A》2001,103(2):176-180
We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early‐onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21‐22 deletions. His HBL was associated with an increasing serum α‐fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12‐27 region. The analysis revealed that the affected chromosome had an 8‐cM deletion within 4q21‐q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21‐q22 that was recently defined in adult hepatocellular carcinomas. © 2001 Wiley‐Liss, Inc. 相似文献
6.
Richard J. Schroer Mary C. Phelan Ron C. Michaelis Eric C. Crawford Steven A. Skinner Michael Cuccaro Richard J. Simensen Janet Bishop Cindy Skinner Don Fender Roger E. Stevenson 《American journal of medical genetics. Part A》1998,76(4):327-336
Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABAA receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother. Am. J. Med. Genet. 76:327–336, 1998. © 1998 Wiley-Liss, Inc. 相似文献
7.
Manifestation of recessive combined D‐2‐, L‐2‐hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome
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Mariko Eguchi Erina Ozaki Toshifumi Yamauchi Masaaki Ohta Takashi Higaki Kiyoshi Masuda Issei Imoto Eiichi Ishii Minenori Eguchi‐Ishimae 《American journal of medical genetics. Part A》2018,176(2):351-358
8.
Anastasia Gazou Angelika Riess Ute Grasshoff Karin Schäferhoff Michael Bonin Anna Jauch Olaf Riess Andreas Tzschach M.D. 《American journal of medical genetics. Part A》2013,161(4):860-864
Mutations or deletions of ACSL4 (FACL4, OMIM 300157) are a rare cause of non‐syndromic X‐linked intellectual disability. We report on a 10‐year‐old male patient with moderate intellectual disability, sensorineural hearing loss, facial dysmorphism, pyloric stenosis, and intestinal obstruction in whom a de novo Xq22.3–q23 deletion was detected by SNP array analysis. The deleted 1.56 Mb interval harbored ACSL4 and eight neighboring genes (GUCY2F, NXT2, KCNE1L, TMEM164, MIR3978, AMMECR1, SNORD96B, and RGAG1). In contrast to previously reported patients with chromosome aberrations in the region of the AMME complex (Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis, OMIM 300194), this deletion did not contain the Alport syndrome gene COL4A5, suggesting that loss of one or several of the other genes in this interval is responsible for the clinical problems. In summary, the patient reported here broadens our knowledge of the phenotypic consequences of deletions of chromosome region Xq22.3–q23 and provides further proof for ACSL4 as an X‐linked intellectual disability gene. © 2013 Wiley Periodicals, Inc. 相似文献
9.
Yi Liu Yanqing Zhang Mehdi Zarrei Rui Dong Xiaomeng Yang Dongmei Zhao Stephen W. Scherer Zhongtao Gai 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2020,183(4):217-226
Chromosome 15q24 microdeletion syndrome is characterized by developmental delay, facial dysmorphism, hearing loss, hypotonia, recurrent infection, and other congenital malformations including microcephaly, scoliosis, joint laxity, digital anomalies, as well as sometimes having autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we report a boy with a 2.58‐Mb de novo deletion at chromosome 15q24. He is diagnosed with ASD and having multiple phenotypes similar to those reported in cases having 15q24 microdeletion syndrome. To delineate the critical genes and region that might be responsible for these phenotypes, we reviewed all previously published cases. We observe a potential minimum critical region of 650 kb (LCR15q24A‐B) affecting NEO1 among other genes that might pertinent to individuals with ASD carrying this deletion. In contrast, a previously defined minimum critical region downstream of the 650‐kb interval (LCR15q24B‐D) is more likely associated with the developmental delay, facial dysmorphism, recurrent infection, and other congenital malformations. As a result, the ASD phenotype in this individual is potentially attributed by genes particularly NEO1 within the newly proposed critical region. 相似文献
10.
Francesco Nicita Fiorenza Ulgiati Laura Bernardini Giacomo Garone Laura Papetti Antonio Novelli Alberto Spalice 《Annals of human genetics》2015,79(3):209-217
Deletions in the 9q33‐q34 region have been reported in patients with early onset epileptic encephalopathy, but a consistent phenotype has yet to emerge. We report on the diagnosis of a de novo 9q33‐q34.12 microdeletion of 4 Mb in a 15‐month‐old girl presenting with severe psychomotor delay, facial dysmorphisms, thin corpus callosum and early myoclonic encephalopathy. This deletion encompasses 101 RefSeq genes, including the four autosomal dominant genes STXBP1, SPTAN1, ENG and TOR1A. We discuss genetic, clinical and epileptic features comparing our patient with those previously reported in the literature. 相似文献
11.
M. J. M. Nowaczyk I. E. Teshima J. Siegel-Bartelt J. T. R. Clarke 《American journal of medical genetics. Part A》1997,69(4):400-405
We report on 2 patients with de novo proximal interstitial deletions of the long arm of chromosome 4: in one the deletion resulted in monosomy (4)(q21.3q23), in the other it produced monosomy (4)(q13.2q23). Review of 9 cases of deletions involving the 4q21/4q22 region reported previously detected a characteristic phenotype in S patients. This phenotype was present in our patients. We conclude that the deletion in the 4q21/4q22 region results in a specific clinical syndrome associated with central nervous system overgrowth that may be a result of anomalous imprinting in the 4q21/4q22 region. Am. J. Med. Genet. 69:400–405, 1997. © 1997 Wiley-Liss, Inc. 相似文献
12.
《European journal of medical genetics》2017,60(4):220-223
Interstitial deletions of the long arm of chromosome 12 are rare and only few cases have been reported in literature so far, with different phenotypic features related to size and gene content of deleted regions. Five patients reported a 12q15-q21 deletion, sharing a 1.3 Mb small region of overlap (SRO) and presenting with developmental delay, nasal speech and mild dysmorphic features.We identified by microarray analysis a new case of 12q15 deletion. Our patient clinical features allow the refinement of the SRO to CNOT2, KCNMB4, and PTPRB genes, improving genotype-phenotype correlations. 相似文献
13.
Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with a 15q26.3 deletion excluding the IGF1R gene
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András Szabó Márta Czakó Kinga Hadzsiev Balázs Duga Zsolt Bánfai Katalin Komlósi Béla Melegh 《American journal of medical genetics. Part A》2018,176(2):443-449
14.
Tomoko Uehara Toshiki Takenouchi Yu Yamaguchi Yumi Daimon Hisato Suzuki Yuri Sakaguchi Kenjiro Kosaki 《American journal of medical genetics. Part A》2019,179(4):659-662
Chromosome 12q15 microdeletion syndrome is characterized by intellectual disability and dysmorphic facial features, but the associations between each of the deleted genes and the phenotypes of 12q15 microdeletion syndrome remain unclear. Recently, the smallest region of overlap in 16 previously reported patients was used to define three candidate genes for the 12q15 microdeletion syndrome: CNOT2, KCNMB4, and PTPRB. Among these three candidate genes, CNOT2 maintains the structural integrity of the carbon catabolite repressor 4 (CCR4)‐negative on TATA (NOT) complex, which plays a key role in regulating global gene expression, and is essential for the enzymatic activity of the CCR4‐NOT complex. Disruption of the CCR4‐NOT complex results in dysregulation of global gene expression, and is associated with various human disease processes, including neuronal diseases. Therefore, CNOT2 haploinsufficiency might account for the neurological features of the 12q15 microdeletion syndrome. Herein, we document a 12‐year ‐ old female patient with mild intellectual disability and multiple structural abnormalities including cleft lip and palate and 2–3 toe syndactyly. She exhibited dysmorphic facial features such as upslanting and short palpebral fissures, micrognathia, low‐set ears, and hypoplastic antihelix. A microarray analysis showed a de novo 1.32‐Mb deletion within 12q15 that included CNOT2 and 14 other genes. Remapping of the 12q15 deletion region in the 16 previously reported patients together with that in the newly identified patient indicated that CNOT2 is the only gene that is commonly deleted. These findings suggest that CNOT2 is the prime candidate for the neurological phenotypes of the 12q15 microdeletion syndrome. 相似文献
15.
Viola Alesi Sara Loddo Federica Calì Valeria Orlando Silvia Genovese Daniele Ferretti Chiara Calacci Giusy Calvieri Roberto Falasca Lucia Ulgheri Fabrizio Drago Bruno Dallapiccola Anwar Baban Antonio Novelli 《American journal of medical genetics. Part A》2019,179(8):1615-1621
Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms. 相似文献
16.
Pietro Cavalli Daniela Giardino Giulietta Gottardi Federica Natacci Salvatore Savasta Lidia Larizza 《American journal of medical genetics. Part A》2001,104(2):157-164
We describe the case of a 15‐year‐old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21–22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI‐7732 and WI‐607, with WI‐7396 and WI‐8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis. 相似文献
17.
Oliver Bartsch Oivi Uibo Piret Laidre 《American journal of medical genetics. Part A》2002,108(4):322-326
We describe here a 3‐year‐old girl demonstrating combined cellular immunodeficiency of B‐ and T‐cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3‐qter and trisomy 8q24.3‐qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one‐third to one‐half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23‐q24 region. Our case narrows down the critical interval for thrombo‐ or pancytopenia to 11q23.3‐q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24‐q25 and/or the ETS‐1 proto‐oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B‐ and T‐lymphocytes) in our patient. © 2002 Wiley‐Liss, Inc. 相似文献
18.
Goizet C Excoffier E Taine L Taupiac E El Moneim AA Arveiler B Bouvard M Lacombe D 《American journal of medical genetics》2000,96(6):839-844
Autism is a rare neurodevelopmental disorder with a strong genetic component. Co-occurrence of autism and chromosomal abnormalities is useful to localize candidate regions that may include gene(s) implicated in autism determinism. Several candidate chromosomal regions are known, but association of chromosome 22 abnormalities with autism is unusual. We report a child with autistic syndrome and a de novo 22q13.3 cryptic deletion detected by FISH. Previously described cases with 22q13.3 deletions shared characteristic developmental and speech delay, but autism was not specifically reported. This case emphasizes a new candidate region that may bear a gene involved in autism etiopathogenesis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:839-844, 2000. 相似文献
19.
Andrey Shuvarikov Ian M. Campbell Piotr Dittwald Nicholas J. Neill Martin G. Bialer Christine Moore Patricia G. Wheeler Stephanie E. Wallace Deborah Terespolsky Sandi Sodhi Matteo Cassina David Viskochil Billur Moghaddam Kristin Herman Chester W. Brown Christine R. Beck Anna Gambin Sau Wai Cheung Ankita Patel Allen N. Lamb Jay W. Ellison J. Britt Ravnan Paweł Stankiewicz Jill A. Rosenfeld 《Human mutation》2013,34(10):1415-1423
We describe the molecular and clinical characterization of nine individuals with recurrent, 3.4‐Mb, de novo deletions of 3q13.2–q13.31 detected by chromosomal microarray analysis. All individuals have hypotonia and language and motor delays; they variably express mild to moderate cognitive delays (8/9), abnormal behavior (7/9), and autism spectrum disorders (3/9). Common facial features include downslanting palpebral fissures with epicanthal folds, a slightly bulbous nose, and relative macrocephaly. Twenty‐eight genes map to the deleted region, including four strong candidate genes, DRD3, ZBTB20, GAP43, and BOC, with important roles in neural and/or muscular development. Analysis of the breakpoint regions based on array data revealed directly oriented human endogenous retrovirus (HERV‐H) elements of ~5 kb in size and of >95% DNA sequence identity flanking the deletion. Subsequent DNA sequencing revealed different deletion breakpoints and suggested nonallelic homologous recombination (NAHR) between HERV‐H elements as a mechanism of deletion formation, analogous to HERV‐I‐flanked and NAHR‐mediated AZFa deletions. We propose that similar HERV elements may also mediate other recurrent deletion and duplication events on a genome‐wide scale. Observation of rare recurrent chromosomal events such as these deletions helps to further the understanding of mechanisms behind naturally occurring variation in the human genome and its contribution to genetic disease. 相似文献
20.
Anatole Laleye Daniele Delneste Olivier Pradier Christine Hans Raphaël Darboux Gonul Ogur 《American journal of medical genetics. Part A》2002,110(2):170-175
Here we report the association of giant platelets and an increase in platelet volume in a 19‐month‐old black female with de novo del 11q24‐qter. The deletion, which was visible on karyotype, was further confirmed and more precisely localized by fluorescence in situ hybridization studies (FISH) that showed the deletion to lie distal to the MLL gene region (11q23). Clinically, the case presented less severe symptoms than Jacobsen syndrome‐the well known partial deletion of the distal end of chromosome 11. Platelet glycoproteins CD 41, CD 42a, C 42b, CD 61, and PAC‐1 were also assayed and found to be normally expressed. To our knowledge, giant platelets are described for the first time in the relevant deleted region. © 2002 Wiley‐Liss, Inc. 相似文献