[Show abstract][Hide abstract] ABSTRACT: Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result in a virtual lack of glycosylation of α-dystroglycan. Compound heterozygous LARGE mutations have been reported in a single human patient, manifesting with mild congenital muscular dystrophy (CMD) and severe mental retardation. These mutations are likely to retain some residual LARGE glycosyltransferase activity as indicated by residual α-dystroglycan glycosylation in patient cells. We hypothesized that more severe LARGE mutations are associated with a more severe CMD phenotype in humans. Here we report a 63-kb intragenic LARGE deletion in a family with Walker-Warburg syndrome (WWS), which is characterized by CMD, and severe structural brain and eye malformations. This finding demonstrates that LARGE gene mutations can give rise to a wide clinical spectrum, similar as for other genes that have a role in the post-translational modification of the α-dystroglycan protein.
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The online version of this article (doi:10.1007/s00439-007-0362-y) contains supplementary material, which is available to authorized users.
Human Genetics 08/2007; 121(6):685-90. DOI:10.1007/s00439-007-0362-y · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We ascertained a patient with the full-blown phenotype of isolated sulfite oxidase deficiency in a consanguineous Arab family. The proband's phenotype included the presence of intractable seizures in the neonatal period, some dysmorphic features, neuroradiologic findings reminiscent of hypoxic ischemic encephalopathy and rapidly progressive brain destruction leading to severe neurodevelopmental impairment. Biochemically, the patient excreted a large amount of S-sulfocysteine with normal amounts of xanthene and hypoxanthine and had normal plasma uric acid, which was consistent with isolated sulfite oxidase deficiency. We report the identification of the first Arab mutation in SUOX, the gene for sulfite oxidase enzyme, in the ascertained family. The newly identified Arab mutation in the SUOX gene (a single nucleotide deletion, del G1244) is predicted to cause a frame shift at amino acid 117 of the translated protein with the generation of a stop codon and total truncation of the molybdo-pterin- and the dimerizing-domain(s) of SUOX protein expressed from the mutant allele. The identification of this new Arab SUOX mutation should facilitate pre-implantation genetic diagnosis and selection of unaffected embryos for future pregnancy in the ascertained family with the mutation and related families with the same mutation.
American Journal of Medical Genetics Part A 07/2005; 136(2):205-9. DOI:10.1002/ajmg.a.30796 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although intravenous immunoglobulin G (IVIG) therapy has been reported in hyperbilirubinemia of Rh hemolytic disease, its use in ABO hemolytic disease has been reported in only a few studies. In our institute we have observed that almost 30% of babies with hyperbilirubinemia due to ABO hemolytic disease required exchange transfusion.
To determine whether administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease would reduce the need for exchange transfusion as a primary goal in these babies.
This was a prospective study involving all newborns with significant hyperbilirubinemia due to direct Coombs-positive ABO hemolytic disease.
All healthy term babies with ABO hemolytic disease with positive direct Coombs test in the period between 2000 and 2002 were identified. Significant hyperbilirubinemia was defined as hyperbilirubinemia requiring phototherapy and/or rising by 8.5 micromol/l per h (0.5 mg/dl per h) or more to require exchange transfusion. Babies were randomly assigned into two groups: group 1 (study group) received phototherapy plus IVIG (500 mg/kg); and group 2 (control group) received phototherapy alone. Exchange transfusion was carried out in any group if at any time the bilirubin level reached 340 micromol/l (20 mg/dl) or more, or rose by 8.5 micromol/l per h (0.5 mg/dl per h) in group 2.
A total of 112 babies were enrolled over 2 years, 56 in each group. Exchange transfusion was carried out in four babies in the study group, while 16 babies in the control group required exchange. Late anemia was not of concern in either group. No adverse effects related to IVIG administration were recorded.
Administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb's test reduces the need for exchange transfusion without producing immediate adverse effects.
Journal of Maternal-Fetal and Neonatal Medicine 10/2004; 16(3):163-6. DOI:10.1080/14767050400009873 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of a low birth weight asymmetrical small for gestational age baby, who presented at the age of 20 hours with sudden abdominal distension. Since birth he has been breastfed and was kept with his mother. Absence of radiological findings of necrotizing enterocolitis or perforation at the time of presentation delayed the diagnosis for 48 hours. At laparotomy the baby was found to have perforation of the stomach with no evidence of other gastrointestinal disorder.
Saudi medical journal 12/2000; 21(11):1085-7. · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a girl with physical anomalies, accelerated skeletal maturation, failure to thrive, and respiratory difficulties consistent with a diagnosis of Marshall-Smith syndrome (MSS). Chromosome analysis showed an inverted duplication of chromosome 2 [46,XX,inv dup(2)(q37q32) de novo] identified by G banding and confirmed by FISH. Several cases of trisomy 2q3 have been reported and established a syndrome, but the present case is the first to be associated with accelerated skeletal maturation and a clinical picture resembling MSS. This raises the possibility that the cause of MSS involves the q3 region of chromosome 2. Few reports of MSS include study of the karyotype, although the chromosomes were apparently normal in those cases where they have been examined. We suggest that karyotyping be undertaken with particular attention to the 2q3 region in patients with suspected MSS. It also would be prudent to assess bone age in all children with trisomy 2q.
American Journal of Medical Genetics 08/1999; 85(2):185-8. DOI:10.1002/(SICI)1096-8628(19990716)85:2<185::AID-AJMG16>3.0.CO;2-W · 3.23 Impact Factor