共查询到20条相似文献,搜索用时 15 毫秒
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Julie S. Fryburg Kant Y. Lin Wendy L. Golden 《American journal of medical genetics. Part A》1996,62(3):274-275
This report is on a 14-month-old boy with manifestations of Opitz (G/BBB) syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested because of some findings in this patient reminiscent of velocardiofacial (VCF) syndrome. The extent of aspiration and of respiratory symptoms in this child is not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one on Xp, the other on 22q11.2. © 1996 Wiley-Liss, Inc. 相似文献
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Titomanlio L Romano A Conti A Genesio R Salerno M De Brasi D Nitsch L Del Giudice E 《American journal of medical genetics. Part A》2004,(2):197-200
Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients. 相似文献
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Miriam G. Wilson O. Modebe Joseph W. Towner S. Douglas Frasier Ming S. Lin John M. Opitz 《American journal of medical genetics. Part A》1983,14(3):567-576
The full phenotype of the Ullrich-Turner syndrome (UTS) is thought to be due to loss of the short arm of X. We report a 16-year-old girl with lack of secondary sexual development, amenorrhea, and short stature. She had thyroiditis and numerous other UTS manifestations and was found to have a non-mosaic 46,X,del(Xp) chromosome abnormality. Breakpoints occurred at p11.4 and p22.31, with a loss of the intervening segment. 相似文献
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Mutations in the MID1 gene are responsible for the X-linked form of Opitz G/BBB syndrome (OS), a disorder that affects the development of midline structures. OS is characterized by hypertelorism, hypospadias, laryngo-tracheo-esophageal (LTE) abnormalities, and additional midline defects. Cardiac, anal, and neurological defects are also present. The expressivity of OS is highly variable, even within the same family. We reviewed all the MID1 mutations reported so far, in both familial and sporadic cases. The mutations are scattered along the entire length of the gene and consist of missense and nonsense mutations, insertions and deletions, either in-frame or causing frameshifts, and deletions of either single exons or the entire MID1 coding region. The variety of described mutations and the lack of a strict genotype-phenotype correlation confirm the previous suggestion of the OS phenotype being caused by a loss-of-function mechanism. However, although a specific mutation cannot entirely account for the observed phenotype, we observed preferential association between some types of mutation and specific clinical manifestations, e.g., brain anatomical defects and truncating mutations. This may suggest that the pathogenetic mechanism underlying the OS phenotype is more complex and may vary among the affected organs. 相似文献
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Engbers H van der Smagt JJ van 't Slot R Vermeesch JR Hochstenbach R Poot M 《European journal of human genetics : EJHG》2009,17(1):129-132
We report on a patient with developmental delay and several facial characteristics reminiscent of Wolf-Hirschhorn syndrome, who carries a terminal 4p16.3 deletion of minimally 1.691 Mb and maximally 1.698 Mb. This deletion contains the FGFRL1 gene, but does not include the WHSC1 gene. Given its expression pattern and its involvement in bone and cartilage formation during embryonic development, the FGFRL1 gene represents a plausible candidate gene for part of the facial characteristics of Wolf-Hirshhorn syndrome in 4p16.3 deletion patients. 相似文献
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Nathaniel H. Robin John M. Opitz Maximilian Muenke 《American journal of medical genetics. Part A》1996,62(3):305-317
Opitz G/BBB syndrome (OS) was first described in 1969 as two separate disorders, the G syndrome, and the BBB syndrome. Since the time, it has become apparent that the BBB and the G syndromes are in fact a single entity, now named the Opitz G/BBB syndrome. However, our recent molecular genetic mapping studies have shown that OS is an heterogeneous disorder, with loci at Xp22 and 22q. To determine if there are any discernible phenotypic differences between the X-linked and the autosomal dominant forms of OS, we have conducted a clinical study of the families who participated in the linkage analysis. In addition, we compared the clinical findings in the study families with those who have been reported in the literature. We found that anterveted nares and posterior pharyngeal cleft were seen only in X-linked families. However, all other manifestations of OS, such as hypertelorism, swallowing difficulties, hypospadias, and developmental delay, were seen in both groups. Therefore, while OS is heterogenous, significant clinical overlap is present between the two groups, and it is presently impossible to assign a specific phenotype to the X-linked or the autosomal type of OS. Furthermore, we found that for individuals in our study families who carried the OS allele, the incidence of major abnormalities was lower than what is reported in the literature. © 1996 Wiley-Liss, Inc. 相似文献
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Bruno Dallapiccola Paola Mandich Emilia Bellone Angelo Selicorni Vahe Mokin Franco Ajmar Giuseppe Novelli 《American journal of medical genetics. Part A》1993,47(6):921-924
We report on molecular studies in 7 patients with Wolf-Hirschhorn syndrome (WHC) not showing an obvious chromosome 4p deletion. Analysis of a set of polymorphic probes mapping in the 4p16.3 region showed the absence of paternal haplotypes in 5 cases, and maternal haplotypes in 2. These observations corroborate evidence for preferential paternal origin of the de novo 4p chromosome deletion. The overall results of molecular studies suggest that the preponderance of paternally derived WHC could be due, rather than to imprinting of this region, to an excess of structural rearrangements in the male meiosis, related to differences between the mechanisms of sperm and egg production. © 1993 Wiley-Liss, Inc. 相似文献
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Zollino M Wright TJ Di Stefano C Tosolini A Battaglia A Altherr MR Neri G 《American journal of medical genetics》1999,82(5):371-375
Chromosome imbalance affecting the short arm of chromosome 4 results in a variety of distinct clinical conditions. Most of them share a number of manifestations, such as mental retardation, microcephaly, pre- and post-natal growth retardation, anteverted and low-set ears, that can be considered as nonspecific signs, generally attributable to gene dosage impairment. On the other hand, more distinctive phenotypic traits correlate with the segmental aneuploidy. Duplications of the distal half of 4p give rise to the partial trisomy 4 syndrome, characterized by a "boxer" nose configuration and deep-set eyes. These signs are usually observed even in cases of small terminal duplications. Haploinsufficiency of 4p16.3 results in the so-called Wolf-Hirschhorn (WH) syndrome, a contiguous gene syndrome characterized by maxillary hypoplasia, large and protruding eyes, high nasal bridge, skeletal abnormalities, and midline defects. The smallest overlapping deletion described so far as a cause of this condition is only 165 kb long, suggesting that one or a few genes in this region act as "master" regulators of different developmental pathways. A "tandem" duplication of 4p16.1p16.3 was detected in association with a subtle deletion of 4p16.3pter on the same chromosome in a patient with the WH phenotype. The 3.2 Mb deletion, spanning the genomic region from the vicinity of D4S43 to the telomere, encompasses the recently delimited "WHS critical region" [Wright et al., 1997: Hum. Mol. Genet. 6:317-324]. This unusual chromosome rearrangement resulted in WH phenotype, clinical manifestations of partial 4p trisomy being mild or absent. This observation led us to speculate that the regulatory gene/genes in the critical WH region affect the expression of other genes in a dose-dependent manner. Haploinsufficiency of this region could be more deleterious than various partial trisomies. 相似文献
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Apparent Opitz BBBG syndrome with a partial duplication of 5p 总被引:2,自引:0,他引:2
L G Leichtman A Werner W T Bass D Smith A R Brothman 《American journal of medical genetics》1991,40(2):173-176
We describe a patient with a paracentric inversion and partial duplication of chromosome 5p. In addition this patient presented with a malformation pattern consistent with Opitz BBBG syndrome. This implies that the gene responsible for this single gene defect may be located within this duplicated region. 相似文献
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Hu CH Liu YF Yu JS Ng YY Chen SJ Su PH Chen JY 《American journal of medical genetics. Part A》2012,(4):726-731
Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder that affects development of midline structures and comprises hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene abnormalities include missense, nonsense, and splicing mutations, small insertions, small deletions, and complex rearrangements. Here, we present a patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T相似文献
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Cho HJ Shin MY Ahn KM Lee SI Kim HJ Ki CS Kim JW 《Journal of Korean medical science》2006,21(5):790-793
X-linked Opitz G/BBB syndrome (XLOS; MIM 300000) is a rare multiple congenital anomaly disorder that is characterized by facial anomalies, laryngeal/tracheal/esophageal defects and genitourinary abnormalities. XLOS is caused by mutations in the MID1 gene which encodes a microtubule-associated RING-Bbox-Coiled-coil (RBCC) protein. We recently found a four-year Korean male patient who was suspected of having XLOS. Mutation analysis of the MID1 gene in the patient and his mother demonstrated that the patient had a novel insertion mutation (c.1798_1799-insC), and his mother was a heterozygous carrier of the mutation. After identification of the causative mutation in this family, prenatal diagnosis of two consecutive fetuses were successfully undertaken. This is the first report on a genetically confirmed case of XLOS in Korea. 相似文献
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Flipsen-ten Berg K van Hasselt PM Eleveld MJ van der Wijst SE Hol FA de Vroede MA Beemer FA Hochstenbach PF Poot M 《European journal of human genetics : EJHG》2007,15(11):1132-1138
The Wolf-Hirschhorn syndrome (WHS (MIM 194190)), which is characterized by growth delay, mental retardation, epilepsy, facial dysmorphisms, and midline fusion defects, shows extensive phenotypic variability. Several of the proposed mutational and epigenetic mechanisms in this and other chromosomal deletion syndromes fail to explain the observed phenotypic variability. To explain the complex phenotype of a patient with WHS and features reminiscent of Wolfram syndrome (WFS (MIM 222300)), we performed extensive clinical evaluation and classical and molecular cytogenetic (GTG banding, FISH and array-CGH) and WFS1 gene mutation analyses. We detected an 8.3 Mb terminal deletion and an adjacent 2.6 Mb inverted duplication in the short arm of chromosome 4, which encompasses a gene associated with WFS (WFS1). In addition, a nonsense mutation in exon 8 of the WFS1 gene was found on the structurally normal chromosome 4. The combination of the 4p deletion with the WFS1 point mutation explains the complex phenotype presented by our patient. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletions represents an additional explanation for the phenotypic variability observed in chromosomal deletion disorders. 相似文献
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Madeleine R. MacDonald G. Bradley Schaefer Ann Haskins Olney Marta Tamayo Jaime L. Frías 《American journal of medical genetics. Part A》1993,46(6):706-711
We report the brain magnetic resonance imaging findings in 4 patients with the Opitz BBB/G syndrome. The scans were assessed by subjective interpretation and computerized image analysis. Findings noted in 3 of the 4 patients include hypoplasia or agenesis of the corpus callosum (3 patients), cortical atrophy and ventriculomegaly (3 patients), macro cisterna magna (3 patients), and a wide cavum septum pellucidum (1 patient). One patient had a normal scan. The demonstration of a wide cavum septum pellucidum extends the spectrum of midline brain anomalies (ventral induction defects) reported in this condition. This study along with other recent reports suggests that midline brain anomalies may be frequent findings in Opitz syndrome. © 1993 Wiley-Liss, Inc. 相似文献
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Hsieh EW Vargervik K Slavotinek AM 《American journal of medical genetics. Part A》2008,(18):2337-2345
Opitz G/BBB syndrome is characterized by midline abnormalities such as hypertelorism, cleft palate, and hypospadias. This syndrome is heterogeneous with an X-linked recessive form caused by mutations in the MID1 gene at band Xp22.3. However, mutations in MID1 have only been identified in 47% of familial cases of X-linked Opitz G/BBB syndrome, and 13% of sporadic cases. We performed a phenotype-genotype analysis of a group of nine new patients with clinical characteristics commonly seen in Opitz G/BBB syndrome, and of previously reported patients. We identified a novel mutation in exon 9 of the MID1 gene, c.1941insTGAGTCATCATCC, leading to a premature termination codon at amino acid 514 in a patient with hypertelorism, apparently low-set ears, a short philtrum, bilateral cleft of lip and palate and hypospadias. This mutation affects the PRY domain of the C-terminus of the MID1 protein. 相似文献
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Gruchy N Jacquemont ML Lyonnet S Labrune P El Kamel I Siffroi JP Portnoï MF 《American journal of medical genetics. Part A》2007,(20):2417-2422
Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis. The complete karyotype was: 46,XX,add(2)(p23)dn.ish inv dup del(2)(:p23.2-->p25.3::p25.3-->qter) (wcp2+,N-MYC++,2pter-)dn. We precisely define the extension of both the duplication and the deletion using bacterial artificial chromosomes clones spanning the regions. The size of the inverted duplicated segment was estimated to be 28 Mb, spanning from 2p23.2 to 2p25.3, and an approximately 1.6 Mb segment at 2pter-p25.3 was deleted in the abnormal chromosome. The physical findings noted in our patient include prominent forehead, hypertelorism, flat nasal bridge, and low-set and large ears. In addition, she had congenital heart defect and scoliosis. Her psychomotor development was severely delayed from the beginning. All these clinical features are the same as observed for the typical trisomy 2p23-pter syndrome. The phenotypic effects of the terminal deletion of 2p in addition to the trisomy are discussed. This is the third patient presenting with a severe clinical phenotype and a de novo inv dup del (2p). 相似文献