Masa Syndrome is due to mutations in the neural cell adhesion gene L1CAM
Aarskog-Scott Syndrome: Confirmation of Linkage to the Pericentromeric Region of the X Chromosome
X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene
Fragile X Phenotype in a Patient With a Large De Novo Deletion in Xq27-q28
Localization of Branchio-Oto-Renal (BOR) Syndrome to a 3 Mb Region of Chromosome 8q
Asymmetry of Methylation With FMR-1 Full Mutation in Two 45,X/46,XX Mosaic Females Associated With Normal Intellect
Familial split hand/split foot long bone deficiency does not segregate with markers linked to the SHFD1 locus in 7q21.3-q22.1
Obstetrical and Gynecological Complications in Fragile X Carriers: A Multicenter Study
Pulmonary atresia associated with maternal 22q11.2 deletion: possible parent of origin effect in the conotruncal anomaly face syndrome
Tightly Linked Flanking Microsatellite Markers for the Usher Syndrome Type I Locus on the Short Arm of Chromosome 11
Deletion Involving D15S113 in a Mother and Son Without Angelman Syndrome: Refinement of the Angelman Syndrome Critical Deletion Region
Source: Name: Kevin M. Sweet Address: Greenwood Genetic Center 1 Gregor Mendel Circle Greenwood, SC 29646 Phone #: (803) 941-8100 FAX #: (803) 941-8114
MASA Syndrome is due to mutations in the neural cell adhesion gene L1CAM
Lieve Vits1, Guy Van Camp1, Paul Coucke1, Erik Fransen1, Kristel De Boulle1, Edwin Reyniers1, Bernhard Korn2, Annemarie Poustka2, Golder Wilson3, Connie Schrander-Stumpel4, Robin M. Winter5, Charles Schwartz6, & Patrick J. Willems1
1
Department of Medical Genetics, University of Antwerp -
ULA, 2610 Antwerp, Belgium
2
Deutsches ?, Im Neuenheimer Feld 506, D-6900 Heidelberg 1, Germany
3
Division of Pediatric Genetics and Metabolism, The University of Texas,
Southwestern Medical Center, Dallas, Texas 75235-9063, USA
4
Department of Genetics and Cell Biology, State University of Limburg,
6201 BX Maastricht, The Netherlands
5
Mothercare Unit of Clinical Genetics and Fetal Medicine,
Institute of Child Health, 30 Guilford Street, London WC1N1EH, UK
6
Greenwood Genetic Center, One Gregor Mendel Circle,
Greenwood, South Carolina 29646, USA
MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus. Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation analysis in eight unrelated patients with MASA syndrome. Three different L1CAM mutations were identified: a deletion removing part of the open reading frame and two point mutations resulting in amino acid substitutions. L1CAM, therefore, harbours mutations leading to either MASA syndrome or HSAS, and might be frequently implicated in X-linked mental retardation with or without hydrocephalus.
Nature Genetics 7:July (1994)
Roger E Stevenson, Melanie May, J Fernando Arena, Edward A Millar, Charles I Scott Jr, Richard J Schroer, Richard J Simensen, Herbert A Lubs, and Charles E Schwartz
Greenwood Genetic Center, Greenwood, South Carolina (RES, MM, RJS, RJS, CES), Department of Pediatrics, Division of Genetics, University of Miami, Miami, Florida (JFA, HAL), Shriners Hospitals for Crippled Children, Chicago Unit, Chicago, Illinois (EAM), and AI duPont Institute, Wilmington, Delaware (CIS)
Aarskog-Scott syndrome was tentatively mapped to Xq13 on the basis of an X:8 translocation by Bawle et al. (Am J Med Genet 17:595-602, 1984). A review of the cytogenetics and the use of molecular markers in that family have resulted in revision of the breakpoints of the translocation to Xp11.2 and 8q11.21 (Glover et al., Hum Mol Genet 2:1717-1718, 1993). Two families, including one of the two initial families with Aarskog-Scott syndrome (Scott, BD:OAS VII (6):240-246, 1971), have participated in our study to evaluate the localization of the gene for Aarskog-Scott syndrome to the pericentromeric region of the X chromosome. Using a series of DNA probes, we have been able to confirm linkage to the X chromosome, with multipoint analysis indicating the most likely localization of the gene to be on the proximal short arm. © 1994 Wiley-Liss, Inc.
American Journal of Medical Genetics 52:339-345 (1994)
Monique Jouet1,
André Rosenthal2,
Giles Armstrong1,
John MacFarlane1,
Roger Stevenson3,
Joan Paterson4,
Aďda Metzenberg5,
Victor Ionasescu6,
Karen Temple7,
& Susan Kenwrick1
1
Department of Medicine, University of Cambridge,
Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
2
Institut fÜr Molekulare Biotechnologie, Jena, Germany
3
Greenwood Genetic Center, Greenwood, South Carolina, USA
4
Duncan Guthrie Institute of Medical Genetics, Glasgow, UK
5
Howard Hughes Medical Institute, University of California, San Francisco, USA
6
Department of Pediatrics, University Hospital of Iowa, Iowa City, Iowa, USA
7
Princess Anne Hospital, Southampton, UK
X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1(L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes form part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.
Nature Genetics 7:july (1994)
Susan G Albright, Ave M Lachiewicz, Jack C Tarleton, Kathleen W Rao, Charles E Schwartz, Renee Richie, Michael B Tennison, and Arthur S Aylsworth
Department of Pediatrics (SGA, KWR, MBT, ASA), Pathology (KWR), and Neurology (MBT), and Brain and Development Research Center (KWR, ASA), University of North Carolina at Chapel Hill, Chapel Hill, Department of Pediatrics (AML), Duke University Medical Center, Durham, North Carolina, and Greenwood Genetic Center (JCT, CES, RR), Greenwood, South Carolina
A 2-year-old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27-q28 including deletion of FMR-1. Molecular analysis of the patient was recently described in Tarleton et al. (1993: Hum Mol Genet 2(11):1973-1974) and the deletion was estimated to be at least 3 megabases (Mb). His mother has 2 FMR-1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a do novo event. The patient does not appear to have clinical or laboratory findings other that those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies. © 1994 Wiley-Liss, Inc.
American Journal of Medical Genetics 51:294-297 (1994)
Greenwood Genetics Center, Greenwood, SC (YW, RJS, RES, CES), National Birth Defects Center, Franciscan Children's Hospital, Boston, MA (KT, JEO), Department of Genetics, Beth Isreal Hospital, Boston, MA (KT)
Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Zmax=3.91 and Zmax=2.83 respectively at Q=0.00). These markers are within 1 cM of one another. Multipoint analysis involving 7 loci, placed the gene between these markers, with a lod-1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279. © 1994 Wiley-Liss, Inc.
American Journal of Medical Genetics 51:169-175 (1994)
Lawrence R Shapiro, Richard J Simensen, Patrick L Wilmot, Gene S Fisch, Betsy K Vibert, Raymond G Fenwick, Jack Tarleton, and Mary Catherine Phelan
Departments of Pediatrics and Pathology (LRS, PLW), New York Medical College and Westchester County Medical Center, Valhalla, Regional Medical Genetics Laboratory (LRS, PLW, BKV), Thiells, and Department of Psychiatry, Kings County Hospital and SUNY/Health Science Center (GSF), Brooklyn, New York; Benton M Montgomery Center for Family Medicine, Self Memorial Hospital (RJS) and Greenwood Genetic Center (JT, RJS, MCP), Greenwood, South Carolina; and Collaborative Diagnostics (RGF), Waltham, Massachusetts
The full FMR-1 mutation is known to cause the fragile X syndrome (Fra(X)), but variable expression in females, including normal to deficient intellect, may be related to random X-inactivation (lyonization). We have evaluated 2 mosaic 45,X/46,XX females who are cytogenetically fra(X) positive, have an FMR-1 full mutation, and are of normal intellect. There were 50% fra(X) chromosomes in the 45,X cells of one of the females; this has not been reported previously. In both patients, there was a strong asymmetry of FMR-1 methylation with the normal allele being totally or 90% unmethylated and the mutant allele being similarly methylated. Thus, the apparent selective inactivation of the full mutant FMR-1 allele appears to have resulted in limited expression with normal intellect. The presence of the fra(X) chromosome in 45,X cells is unique; however, there may be no relationship to the asymmetric inactivation of the mutant allele which could be due to chance or a mechanism yet to be delineated. © Wiley-Liss, Inc.
American Journal of Medical Genetics 51:507-508 (1994)
Jean-Christophe Marinoni,
Ellen Boyd1,
Stephanie Sherman2,
and Charles Schwartz
Greenwood Genetic Center, Greenwood, SC 29646,
1
Mission Genetic Center, Asheville, NC 28801 and
2
Division of Genetics and Molecular Medicine, Emory University, Atlanta, GA 30322, USA
Ectrodactyly (split hand/split foot, SHSF) is characterized by the absence of middle rays of the hand or the foot. Cytogenetic analyses of some of the cases have indicated an association between chromosomal rearrangements involving 7q21.3-q22 and ectrodactyly. Based on these observations, an autosomal dominant form of ectrodactyly is assumed to reside in this region and the locus has been designated SHFD1 (split hand/split foot disorder). Here we report a large family where split hand/split foot long bone deficiency (SHFLD)segregates in an autosomal dominant mode. Linkage analysis, using microsatellite markers located in 7q21-q22, excludes this region from containing the gene responsible for SHFLD in this family. These results would appear to indicate genetic heterogeneity exists in autosomal dominant SHSF.
Human Molecular Genetics 3(8):1355-1357 (1994)
Greenwood Genetic Center, Greenwood (CES, JD, RES), South Carolina; Genetics and IVF Institute, Fairfax, and Medical College of Virginia, Richmond (PNH-P), Virginia; John F. Kennedy Institute, Glostrup, (MB, MM, NT), Denmark; Children's Hospital, Denver (CH, RH), Colorado; and Ongwanada Resource Centre, Kingston (JJAH), Ontario, Canada
We have conducted a multicenter obstetrical and gynecological survey of women in fragile X families. Included in the study were 131 gene carriers (39 with a full mutation and 92 with a premutation) and 109 noncarriers. Analysis indicated that higher numbers of fragile X gene carriers reported having irregular menses and other gynecological complications. As a group they also experienced cessation of menses prior to age 40 years at a significantly higher rate. The data appear to indicate that the FMR1 gene may play a role in the development and proliferation of oogonia. © 1994 Wiley-Liss, Inc.
American Journal of Medical Genetics 51:400-402 (1994)
Laurie H Seaver, John W Pierpont, Robert P Erickson, Richard L Donnerstein, Suzanne B Cassidy
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona College of Medicine, Tucson, Arizona, USA.
A blind study was designed to test the hypothesis that some persons with a relatively rare cardiac malformation, pulmonary atresia with ventriculoseptal defect (PA/VSD), have a recognisable phenotype. Fourteen patients with cyanotic congenital heart lesions were examined by dysmorphologists blinded to the type of cardiac malformation. Six children were judged to have a similar craniofacial appearance; all had PA/VSD. These children were not originally considered to fall within the classic phenotypes of the DiGeorge sequence or the velocardiofacial syndrome, both of which have been shown to be associated with deletions of 22q11. More recently, 22q11 deletions have been documented in the conotruncal anomaly face syndrome and apparently isolated conotruncal heart defects. A new acronym, CATCH 22 syndrome (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia) has been suggested to encompass this very broad phenotypic spectrum. A preliminary molecular study was conducted using the dinucleotide repeat D22S264 located on chromosome 22q11.2. All cases tested with the subtle but recognisable phenotype had deletions, all lacking the maternal contribution at this locus, suggesting there may be a parent of origin effect.
J Med Genet 1994;31:830-834
BJB Keats, N Nouri, MZ Pelias, PL Deininger, M Litt.
MZ Pelias. "Anencephalic infants as organ donors." Invited Editorial, The Fetus, 4(2):21-23 (1994).
Ron C. Michaelis, Steven A. Skinner, Bonné A. Lethco, Richard J. Simensen, Timothy A. Donlon, Jack Tarleton and Mary C. Phelan
Greenwood Genetic Center, Greenwood, SC (RCM, SAS, BAL, RJS, JT, MCP) and Kapiolani Medical Center for Women and Children, Honolulu, HI (TAD).
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Aarskog-Scott Syndrome: Confirmation of Linkage to the Pericentromeric Region of the X Chromosome
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Fragile X Phenotype in a Patient With a Large De Novo Deletion in Xq27-q28
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Localization of Branchio-Oto-Renal (BOR) Syndrome to a 3 Mb Region of Chromosome 8q
Y Wang, K Treat, RJ Schroer, JE O'Brien, RE Stevenson and CE Schwartz
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Asymmetry of Methylation With FMR-1 Full Mutation in Two 45,X/46,XX Mosaic Females Associated With Normal Intellect
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Familial split hand/split foot long bone deficiency does not segregate with markers linked to the SHFD1 locus in 7q21.3-q22.1
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Obstetrical and Gynecological Complications in Fragile X Carriers: A Multicenter Study
CE Schwartz, J Dean, PN Howard-Peebles, M Bugge, M Mikkelsen, N Tommerup, C Hull, R Hagerman, JJA Holden, and RE Stevenson
Source: Name: Kevin M. Sweet
Address: Greenwood Genetic Center
1 Gregor Mendel Circle
Greenwood, SC 29646
Phone #: (803) 941-8100
FAX #: (803) 941-8114
Pulmonary atresia associated with maternal 22q11.2 deletion: possible parent of origin effect in the conotruncal anomaly face syndrome
Source: Name: Mary Z. Pelias, PhD, JD
Address: Department of Biometry and Genetics
LSU Medical Center
1901 Perdido Street
New Orleans, LA 70112
Phone: (504) 568-6151
FAX: (504) 568-8500
"Tightly Linked Flanking Microsatellite Markers for the Usher Syndrome Type I Locus on the Short Arm of Chromosome 11."
Am J Hum Genet, 54:681-686 (1994).
Source: Name: Ron Michaelis
Address: Greenwood Genetic Center
Phone: (803) 941-8100
FAX: (803) 941-8133
Deletion Involving D15S113 in a Mother and Son Without Angelman Syndrome: Refinement of the Angelman Syndrome Critical Deletion Region.
