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A Aylsworth

Publications and source records attributed to A Aylsworth.

10 recordsLinked to original sources
PubMed2005

Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10.

Neural tube defects (NTDs) are the second most common birth defects (1 in 1000 live births) in the world. Periconceptional maternal folate supplementation reduces NTD risk by 50-70%; however, studies of folate related and other developmental genes in humans have failed to definitively identify a major causal gene for NTD. The aetiology of NTDs remains unknown and both genetic and environmental factors are implicated. We present findings from a microsatellite based screen of 44 multiplex pedigrees ascertained through the NTD Collaborative Group. For the linkage analysis, we defined our phenotype narrowly by considering individuals with a lumbosacral level myelomeningocele as affected, then we expanded the phenotype to include all types of NTDs. Two point parametric analyses were performed using VITESSE and HOMOG. Multipoint parametric and nonparametric analyses were performed using ALLEGRO. Initial results identified chromosomes 7 and 10, both with maximum parametric multipoint lod scores (Mlod) >2.0. Chromosome 7 produced the highest score in the 24 cM interval between D7S3056 and D7S3051 (parametric Mlod 2.45; nonparametric Mlod 1.89). Further investigation demonstrated that results on chromosome 7 were being primarily driven by a single large pedigree (parametric Mlod 2.40). When this family was removed from analysis, chromosome 10 was the most interesting region, with a peak Mlod of 2.25 at D10S1731. Based on mouse human synteny, two candidate genes (Meox2, Twist1) were identified on chromosome 7. A review of public databases revealed three biologically plausible candidates (FGFR2, GFRA1, Pax2) on chromosome 10. The results from this screen provide valuable positional data for prioritisation of candidate gene assessment in future studies of NTDs.

Chromosomes, Human, Pair 10↗
PubMed1997

The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2.

OBJECTIVE: Neurofibromatosis 1 and neurofibromatosis 2 are autosomal dominant genetic disorders in which affected individuals develop both benign and malignant tumors at an increased frequency. Since the original National Institutes of Health Consensus Development Conference in 1987, there has been significant progress toward a more complete understanding of the molecular bases for neurofibromatosis 1 and neurofibromatosis 2. Our objective was to determine the diagnostic criteria for neurofibromatosis 1 and neurofibromatosis 2, recommendations for the care of patients and their families at diagnosis and during routine follow-up, and the role of DNA diagnostic testing in the evaluation of these disorders. DATA SOURCES: Published reports from 1966 through 1996 obtained by MEDLINE search and studies presented at national and international meetings. STUDY SELECTION: All studies were reviewed and analyzed by consensus from multiple authors. DATA EXTRACTION: Peer-reviewed published data were critically evaluated by independent extraction by multiple authors. DATA SYNTHESIS: The main results of the review were qualitative and were reviewed by neurofibromatosis clinical directors worldwide through an Internet Web site. CONCLUSIONS: On the basis of the information presented in this review, we propose a comprehensive approach to the diagnosis and treatment of individuals with neurofibromatosis 1 and neurofibromatosis 2.

Genes, Neurofibromatosis 1↗
PubMed1997

X-linked situs abnormalities result from mutations in ZIC3.

Vertebrates position unpaired organs of the chest and abdomen asymmetrically along the left-right (LR) body axis. Each structure comes to lie non-randomly with respect to the midline in an overall position designated situs solitus, exemplified in humans by placement of the heart, stomach and spleen consistently to the left. Aberrant LR axis development can lead to randomization of individual organ position (situs ambiguus) or to mirror-image reversal of all lateralized structures (situs inversus). Previously we mapped a locus for situs abnormalities in humans, HTX1, to Xq26.2 by linkage analysis in a single family (LR1) and by detection of a deletion in an unrelated situs ambiguus male (Family LR2; refs 2,3). From this chromosomal region we have positionally cloned ZIC3, a gene encoding a putative zinc-finger transcription factor. One frameshift, two missense and two nonsense mutations have been identified in familial and sporadic situs ambiguus. The frameshift allele is also associated with situs inversus among some heterozygous females, suggesting that ZIC3 functions in the earliest stages of LR-axis formation. ZIC3, which has not been previously implicated in vertebrate LR-axis development, is the first gene unequivocally associated with human situs abnormalities.

Amino Acid Sequence↗
PubMed1997

Localization of a gene for oculodentodigital syndrome to human chromosome 6q22-q24.

Oculodentodigital syndrome (ODD) is a congenital, autosomal dominant disorder which affects the development of the face, eyes, limbs and dentition. Spastic paraparesis is thought to be an occasional manifestation of the disorder. Type III syndactyly, which occurs as part of ODD, has also been reported to occur as an isolated entity. In the current investigation, a total genome search for the location of the ODD locus was instigated and linkage to polymorphic markers located on chromosome 6q established (pairwise Zmax = 9.37; theta = 0.001). Analysis of a large family with type III syndactyly, but atypical facial features, further suggested that isolated type III syndactyly is also located in this same region of the genome.

Abnormalities, Multiple↗
PubMed1985

Chromosomal abnormalities associated with congenital contractures (arthrogryposis).

In a study of 350 patients with multiple congenital contractures (arthrogryposis), 80 (23%) patients had mental retardation or were developmentally delayed. Out of that group of 80 patients, 13 (16%) were found to have abnormal karyotypes. Two of the thirteen had a family history of chromosomal abnormalities without congenital contractures, therefore, 11 patients had chromosomal anomalies which appeared to be associated with the congenital contractures. Five of the eleven (45%) had chromosome mosaicism, three of those had tissue mosaicism. Two had abnormal skin fibroblast cell lines and normal peripheral leukocyte chromosome studies and one had a normal bone marrow karyotype with abnormal peripheral leukocyte chromosome studies. Chromosome studies were done in these patients with congenital contractures because of developmental delay and multisystem involvement, or recognition of clinical features typical of a chromosomal syndrome. We recommend first lymphocyte; and if those are normal, then fibroblast studies be done on all patients with multiple joint contractures and developmental delay, particularly if unusual facial features or multisystem abnormalities are present.

Abnormalities, Multiple↗
PubMed1975

Mannosidosis: deficiency of a specific alpha-mannosidase component in cultured fibroblasts.

Evidence is prisented which shows that the enzymatic defect in mannosidosis, the deficiency of alpha-mannosidase, is expressed in cultured skin fibroblasts from patients with mannosidosis. Additionally, by Cellogel electrophoresis, the enzyme can be separated into two major components (a heat stable component missing in mannosidosis fibroblasts with a pH optimum of 3.6-4.0 and a heat labile component present in mannosidosis fibroblasts with a pH optimum of 5.6-6.0). The specific activity and electrophoresis of alpha-mannosidase from cultured amniotic fluid cells are also shown to be similar to cultured skin fibroblasts.

Amniotic Fluid↗