The Experts below are selected from a list of 1758 Experts worldwide ranked by ideXlab platform
Edward R.b. Mccabe - One of the best experts on this subject based on the ideXlab platform.
-
dax1 origin function and novel role
Molecular Genetics and Metabolism, 2005Co-Authors: Kathy K Niakan, Edward R.b. MccabeAbstract:The orphan nuclear receptor NR0B1 encodes the DAX1 protein, which stands for the dosage sensitive sex-reversal (DSS), adrenal hypoplasia congenita (AHC) critical region on the X-chromosome, Gene 1. DAX1 was initially identified as part of a Contiguous Gene Syndrome and is known to function in the proper formation of the adult adrenal gland. It has been hypothesized that DAX1 is responsible for the establishment and maintenance of the steroidogenic axis of development. Recent insight from the murine ortholog Dax1 along with reports of an alternatively spliced variant in humans suggests that Dax1 has additional functional roles beyond those previously understood. Here, we review DAX1/Dax1 known functional roles and the recently hypothesized function in the development of the embryo and in the maintenance of embryonic stem cell pluripotency.
-
il1rapl1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of dax1
Human Mutation, 2004Co-Authors: Yaohua Zhang, Bingling Huang, Kathy K Niakan, Linda L Mccabe, Edward R.b. Mccabe, Katrina M DippleAbstract:IL1RAPL1 (interleukin-1 receptor accessory protein-like, Gene 1) has recently been shown to be mutated in patients with X-linked mental retardation. Clinical experience has suggested that patients with the Contiguous Gene Syndrome, complex glycerol kinase deficiency (cGKD), will have mental retardation (MR) if they have deletions extending from the GK Gene into the DMD Gene and/or involving a significant extension telomeric from DAX1. We examined cell lines from patients with cGKD whose clinical features would be informative and would allow us to determine if IL1RAPL1 deletions can help to explain the MR in patients with deletions extending telomeric from DAX1. Our results showed that nearly all patients with deletions involving DAX1, but not DMD, had MR if IL1RAPL1 was deleted. If ILIRAPLI and DMD were intact, the patients with DAX1 deletions only rarely had normal development. Deletions in DNA from patients with cGKD who exhibited MR and had normal IL1RAPL1 all involved the GK and DMD Genes. Our data are consistent with the association of IL1RAPL1 Gene deletion and MR in the majority of patients with cGKD and deletions extending telomeric from DAX1. © 2004 Wiley-Liss, Inc.
-
AluY insertion (IVS4-52ins316alu) in the glycerol kinase Gene from an individual with benign glycerol kinase deficiency
Human mutation, 2000Co-Authors: Yaohua Zhang, Bingling Huang, Katrina M Dipple, Kim C. Worley, G. Finlayson, B.l. Therrell, Prescott L. Deininger, Edward R.b. MccabeAbstract:Glycerol kinase deficiency has three distinct forms: an isolated form which may be benign or symptomatic, and a complex form which is symptomatic and part of an Xp21 Contiguous Gene Syndrome. Here we report the case of a male with benign isolated glycerol kinase deficiency who was incidentally identified after observation of pseudohypertriglyceridemia. DNA sequencing of this subject's glycerol kinase Gene showed the insertion of an AluY sequence in intron 4 of the glycerol kinase Gene. Although Alu insertions have been implicated in other diseases, and a closely related AluY element is found as an insert in the C1 inhibitor Gene in patients with hereditary angioedema, this is the first case of glycerol kinase deficiency caused by an Alu insertion. Hum Mutat 15:316–323, 2000. © 2000 Wiley-Liss, Inc.
-
Complex glycerol kinase deficiency: A Contiguous Gene Syndrome involving the Duchenne muscular dystrophy, glycerol kinase, and adrenal hypoplasia congenita loci
Mental Retardation and Developmental Disabilities Research Reviews, 1996Co-Authors: Edward R.b. Mccabe, Weiwen Guo, Thomas P. BurrisAbstract:Complex glycerol kinase deficiency is a Contiguous Gene Syndrome that involves deletion of the glycerol kinase (GK) Gene along with the loci for Duchenne muscular dystrophy (DMD) and/or adrenal hypoplasia congenita (AHC). The deletion breakpoints in these patients allowed identification of the critical regions for the GK and AHC Genes, and both were identified using a positional cloning strategy. In addition to complex glycerol kinase deficiency, there are also two distinct phenotypes characterizing isolated glycerol kinase deficiency, the juvenile and benign forms. The juvenile form has onset in the first weeks to years of life with episodic decompensation. These episodes can be prevented or at least reduced in number by the use of a reduced-fat and therefore reduced-glycerol diet. Other families exhibit the benign form of isolated glycerol kinase deficiency. The affected individuals within these families have the biochemical features of this disorder but are asymptomatic. © 1996 Wiley-Liss, Inc.
-
rapid molecular cytoGenetic analysis of x chromosomal microdeletions fluorescence in situ hybridization fish for complex glycerol kinase deficiency
American Journal of Medical Genetics, 1995Co-Authors: Kim C. Worley, Edward R.b. Mccabe, E A Lindsay, W Bailey, J Wise, Antonio BaldiniAbstract:Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring time-consuming and unreliable dosage calculations. In this report, we describe rapid molecular cytoGenetic identification of deleted DNA in affected males with the Xp21 Contiguous Gene Syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. CGKD deletions involve the Genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families, using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase Gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X-chromosomal deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available.
Maria Luisa Martinezfrias - One of the best experts on this subject based on the ideXlab platform.
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.
Laura Rodriguez - One of the best experts on this subject based on the ideXlab platform.
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.
Wolfgang G. Sippell - One of the best experts on this subject based on the ideXlab platform.
-
Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Congenital Adrenal Hypoplasia: Clinical Spectrum, Experience with Hormonal Diagnosis, and Report on New Point Mutations of the DAX-1 Gene
2013Co-Authors: Michael Peter, Carl-joachim Partsch, Matthias Viemann, Wolfgang G. SippellAbstract:X-linked congenital adrenal hypoplasia (AHC) is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the DAX-1 Gene, a recently discovered member of the nuclear hormone receptor superfamily. Hypogonadotropic hypogonadism is frequently associated with AHC. AHC occurs as part of a Contiguous Gene Syndrome together with glycerol kinase deficiency (GKD) and Duchenne’s muscular dystrophy. The present series, collected over the past 2 decades, includes 18 AHC boys from 16 families: 4 with AHC, GKD, and Duchenne’s muscular dystrophy; 2 with AHC and GKD; and 12 with AHC (5 young adults with hypogonadotropic hypogonadism). Most of the boys presented with salt wasting and hyperpigmentation during the neonatal period. Plasma steroid determinations performed in the first weeks of life often showed confusing results, probably caused by steroids produced in the neonates’ persisting fetocortex. Aldosterone deficiency usually preceded cortisol deficiency, which explains why the patients more often presented with salt-wasting rather than with hypoglycemic symptoms. A
-
congenital adrenal hypoplasia clinical spectrum experience with hormonal diagnosis and report on new point mutations of the dax 1 Gene
The Journal of Clinical Endocrinology and Metabolism, 1998Co-Authors: Michael Peter, Carl-joachim Partsch, Matthias Viemann, Wolfgang G. SippellAbstract:X-linked congenital adrenal hypoplasia (AHC) is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the DAX-1 Gene, a recently discovered member of the nuclear hormone receptor superfamily. Hypogonadotropic hypogonadism is frequently associated with AHC. AHC occurs as part of a Contiguous Gene Syndrome together with glycerol kinase deficiency (GKD) and Duchenne's muscular dystrophy. The present series, collected over the past 2 decades, includes 18 AHC boys from 16 families: 4 with AHC, GKD, and Duchenne's muscular dystrophy; 2 with AHC and GKD; and 12 with AHC (5 young adults with hypogonadotropic hypogonadism). Most of the boys presented with salt wasting and hyperpigmentation during the neonatal period. Plasma steroid determinations performed in the first weeks of life often showed confusing results, probably caused by steroids produced in the neonates' persisting fetocortex. Aldosterone deficiency usually preceded cortisol deficiency, which explains why the patients more often presented with salt-wasting rather than with hypoglycemic symptoms. An ACTH test was often necessary to detect cortisol deficiency in the very young infants. In some patients, serial testing was necessary to establish the correct diagnosis. In 4 boys studied during the first 3 months after birth, we found pubertal LH, FSH, and testosterone plasma levels indicating postnatal transient activation of the hypothalamic-pituitary-gonadal axis as in normal boys. Previous studies have shown that the DAX-1 Gene is deleted in the AHC patients with a Contiguous Gene Syndrome and is mutated in nondeletion patients. Most of the point mutations identified in AHC patients were frameshift mutations and stop mutations. In the 15 patients available for molecular analysis of the DAX-1 Gene, there were large deletions in 6 patients and point mutations in another 7 patients. All of the point mutations identified in the present study resulted in a nonfunctional truncated DAX-1 protein. Two brothers with primary adrenal insufficiency and a medical history that strongly suggested AHC had no mutation in the DAX-1 Gene. Thus, additional, as yet unknown Genes must play a part in normal adrenal cortical development.
Marcella Zollino - One of the best experts on this subject based on the ideXlab platform.
-
ocular manifestations in wolf hirschhorn Syndrome
Journal of Aapos, 2009Co-Authors: Anna Dickmann, Rosa Parrilla, Annabella Salerni, Gustavo Savino, Isabella Vasta, Marcella Zollino, Sergio Petroni, Giuseppe ZampinoAbstract:Introduction Wolf-Hirschhorn Syndrome (WHS) multiple congenital anomalies/mental retardation is caused by partial deletion of the short arm of chromosome 4 and can be considered a Contiguous Gene Syndrome, characterized by typical facial appearance, mental retardation, growth delay, and seizures. Methods We investigated the ocular defects in a population of 10 patients with WHS and analyzed the relationship between ocular findings and the extent of deletion on chromosome 4. Results The ocular abnormalities found included hypertelorism, strabismus, refractive errors, epicanthal folds, proptosis, downslanting palpebral fissures, microphthalmos, microcornea, iris coloboma, optic nerve coloboma, ocular cyst, ptosis, glaucoma, and nystagmus. Different breakpoints of the chromosomal rearrangement were observed in individual patients, ranging from 4p15.1 to 4p16.3, and the size of chromosomal deletion ranged from 2.6 to 26 million base pairs. Conclusions Congenital glaucoma and colobomatous ocular cysts have rarely been described in WHS patients that were previously reported. In all cases exhibiting strabismus, an exodeviation was present. Comparing genotype with ocular phenotype, a relationship between the size of deletion and the severity of the ocular involvement was observed in all cases but one.
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
-
the new wolf hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn Syndrome (WHS), is a well known Contiguous Gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to Generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.