Zeigler M

References (4)

Title : Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect - Macarov_2007_J.Intellect.Disabil.Res_51_329
Author(s) : Macarov M , Zeigler M , Newman JP , Strich D , Sury V , Tennenbaum A , Meiner V
Ref : J Intellect Disabil Res , 51 :329 , 2007
Abstract : BACKGROUND: Patients with Xp22.3 interstitial and terminal deletions have been shown to be affected by intellectual disability (ID) or autism. Previously, VCX-A (variably charged protein X-A), located at Xp22.3, was introduced as a gene for ID and its presence was suggested to be sufficient to maintain normal mental development. Recent reports suggest that mutations in NLGN4 (neuroligin 4), located at that same region, are involved in autistic disorders and ID.
METHODS: In the current case study, we clinically and molecularly describe a pedigree of three generations affected by contiguous gene syndrome that includes features of X-linked ichthyosis and Kallmann syndrome.
RESULTS: Molecular analysis revealed the presence of an interstitial deletion spanning approximately 4.5Mb at Xp22.3. The centromeric breakpoint was localized between markers DXS1467 and DXS8051, proximal to KAL-1. The telomeric breakpoint was localized between markers DXS89 and DXS1060, distal to NLGN4. The deletion of VCX-A and NLGN4 in this family prompted us to examine the cognitive functions of our two adult patients using comprehensive intellectual and neurocognitive assessment. Normal intellectual function was found in one patient and mild ID was revealed in the other. Neither patient met any Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for a pervasive developmental disorder such as autism.
CONCLUSIONS: These findings suggest that deletion of VCX-A and NLGN4 can result in variable phenotypic features and that normal mental development can be achieved despite this deletion, emphasizing the importance of environmental factors and possible modifier genes.
ESTHER : Macarov_2007_J.Intellect.Disabil.Res_51_329
PubMedSearch : Macarov_2007_J.Intellect.Disabil.Res_51_329
PubMedID: 17391250

Title : Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation - Stein_2007_Eur.J.Pediatr_166_663
Author(s) : Stein J , Garty BZ , Dror Y , Fenig E , Zeigler M , Yaniv I
Ref : Eur J Pediatr , 166 :663 , 2007
Abstract : Wolman disease is a rapidly fatal lysosomal storage disease caused by the complete absence of lysosomal acid lipase activity. We report the cure of an infant with Wolman disease following transplantation of unrelated HLA-mismatched umbilical cord blood-derived stem cells. Umbilical cord blood was chosen as the stem-cell source because of its immediate availability and reduced tendency to cause graft-versus-host disease. The transplantation resulted in restoration of normal acid lipase levels before the onset of permanent end-organ damage. Four years after transplantation, the patient is thriving and has normal levels of acid lipase in peripheral blood cells. To our knowledge, this is the first report of a successful unrelated cord blood transplant in a patient with Wolman disease. Umbilical cord stem cells transplantation can restore acid lipase levels in Wolman disease, and if performed early, can cure the disease.
ESTHER : Stein_2007_Eur.J.Pediatr_166_663
PubMedSearch : Stein_2007_Eur.J.Pediatr_166_663
PubMedID: 17033804

Title : Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease - Zschenker_2001_J.Lipid.Res_42_1033
Author(s) : Zschenker O , Jung N , Rethmeier J , Trautwein S , Hertel S , Zeigler M , Ameis D
Ref : J Lipid Res , 42 :1033 , 2001
Abstract : Wolman disease results from an inherited deficiency of lysosomal acid lipase (LAL; EC 3.1.1.13). This enzyme is essential for the hydrolysis of cholesteryl esters and triacylglycerols derived from endocytosed lipoproteins. Because of a complete absence of LAL activity, Wolman patients accumulate progressive amounts of cholesteryl esters and triacylglycerols in affected tissues. To investigate the nature of the genetic defects causing this disease, mutations in the LAL gene from three subjects of Moslem-Arab and Russian descent living in Israel were determined. Two homozygotes for a novel 1-bp deletion introducing a premature in-frame termination codon at amino acid position 106 (S106X) were identified. A third subject was a homozygote for a G-5R signal peptide substitution and a G60V missense mutation. The functional significance of these mutations was tested by in vitro expression of single and double mutants in Spodoptera frugiperda cells. Single mutants G60V and S106X and double mutant G-5R/G60V displayed a virtual absence of lipase activity in cell extracts and culture medium. Signal peptide mutant G-5R retained lipase activity in cell extracts and showed a drastically reduced enzyme activity in culture supernatant, indicating that the mutation may affect secretion of active enzyme from cells. These results support the notion that Wolman disease is a genetically heterogeneous disorder of lipid metabolism.
ESTHER : Zschenker_2001_J.Lipid.Res_42_1033
PubMedSearch : Zschenker_2001_J.Lipid.Res_42_1033
PubMedID: 11441129
Gene_locus related to this paper: human-LIPA

Title : Hydrops fetalis in four siblings caused by galactosialidosis -
Author(s) : Landau D , Meisner I , Zeigler M , Bargal R , Shinwell ES
Ref : Isr J Med Sci , 31 :321 , 1995
PubMedID: 7759227
Gene_locus related to this paper: human-CTSA