1/14. Identification of a novel mutation in 3beta-hydroxysteroid-Delta8-Delta7-isomerase in a case of Conradi-Hunermann-Happle syndrome.The X-linked dominant Conradi-Hunermann-Happle (CDPX2, MIM 302960) syndrome belongs to the rare, heterogeneous group of diseases called chondrodysplasia punctata. The disease has been connected recently with deficiency of 3beta-hydroxysteroid-Delta8-Delta7-isomerase (also called emopamil-binding protein, EBP), catalysing an intermediate step in the conversion of lanosterol to cholesterol (1, 2). We report a case of CDPX2 with a new missense mutation (C-->G 439) in exon 4, leading to a R147G aminoacid substitution in the EBP.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/14. Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP.X-linked dominant Conradi-Hunermann-Happle syndrome (CDPX2; MIM 302960) is a rare chondrodysplasia punctata primarily affecting females. CDPX2 is presumed lethal in males, although a few affected males have been reported. CDPX2 is a cholesterol biosynthetic disorder due to 3-beta-hydroxysteroid-delta8,delta7-isomerase deficiency caused by mutations in the emopamil binding protein (EBP) gene. A 2.5-year-old Caucasian male was followed from the age of 6 weeks and noted to have significant developmental delay, hypotonia, seizures, and patchy hypopigmentation. Multiple congenital anomalies included a unilateral cataract, esotropia, crossed renal ectopia, stenotic ear canals, and failure to thrive, requiring G-tube placement. Multiple minor anomalies and ptosis were noted. No skeletal asymmetry or chondrodysplasia punctata were noted on skeletal survey at 6 weeks and 13 months. An extensive genetic work-up including cholesterol (126-176 mg/dl) and 7-dehydrocholesterol was unrevealing. However, the levels of 8(9)-cholestenol and 8-dehydrocholesterol were mildly increased in plasma, which was confirmed in cultured fibroblasts. This prompted molecular analysis of the EBP gene, which revealed a novel hemizygous (nonmosaic) mutation in exon 2 (L18P). Two restriction digests were developed that confirmed this mutation in skin fibroblasts, blood, and buccal cells (all nonmosaic). We determined that the patient's mother (adopted) also has the L18P mutation enabling prenatal diagnosis of a normal male fetus. She has normal stature, no asymmetry, no cataracts at this time, and has a patch of hyperpigmentation on her chest best visualized on Woods lamp examination, characteristic of CDPX2. The mild maternal phenotype has been described previously. However, this nonmosaic missense mutation has resulted in a severe phenotype in her surviving son.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
3/14. fetus with an unusual form of nonrhizomelic chondrodysplasia punctata: case report and review.chondrodysplasia punctata (CDP) is a heterogeneous condition mainly characterized by premature and ectopic calcification of cartilage. Many genetic and nongenetic causes have been described leading to a preliminar etiological classification into defects of peroxisomal metabolism, defects in cholesterol metabolism, and vitamin K (vit K) metabolism. However, numerous cases of CDP still remain unclassified. The difficulties in reaching a causal diagnosis are illustrated here by a 23-week-old fetus with nonrhizomelic CDP characterized by extensive cartilage stippling, brachyphalangy, and nasal hypoplasia.- - - - - - - - - - ranking = 2.8020315005288keywords = vitamin (Clic here for more details about this article) |
4/14. Cervical spine stenosis and possible vitamin k deficiency embryopathy in an unusual case of chondrodysplasia punctata and an updated classification system.We describe in this paper a patient with brachytelephalangic chondrodysplasia punctata (BCDP) who has multiple serious medical problems and striking physical abnormalities. These include cervical spine stenosis with resultant quadriplegia, severe nasal hypoplasia, and brachytelephalangy. Radiographs taken shortly after birth demonstrated extensive epiphyseal and vertebral stippling, and distal phalangeal hypoplasia. The pregnancy was complicated by maternal intestinal obstruction due to a small bowel carcinoma and probable malabsorption. The severity of the phenotype in this case may have been influenced by these maternal factors particularly vitamin k deficiency.- - - - - - - - - - ranking = 19.010157502644keywords = vitamin, deficiency (Clic here for more details about this article) |
5/14. prenatal diagnosis and investigation of a fetus with chondrodysplasia punctata, ichthyosis, and kallmann syndrome due to an Xp deletion.We report the prenatal diagnosis of a male fetus with X-linked recessive chondrodysplasia punctata (CDPX), steroid sulphatase (STS) deficiency, X-linked kallmann syndrome (KAL), and a chromosome deletion at Xp22.31. Biochemical analysis of bone from this case indicates that CDPX is not a defect of vitamin K metabolism. Immunocytochemical study of the brain suggests that KAL is a defect in neuronal migration.- - - - - - - - - - ranking = 3.8020315005288keywords = vitamin, deficiency (Clic here for more details about this article) |
6/14. Severe tracheobronchial stenosis in the X-linked recessive form of chondrodysplasia punctata.The X-linked recessive form of chondrodysplasia punctata, characterized by chondrodysplasia and punctate calcification of cartilage, is caused by a defect in the vitamin K-dependent enzyme arylsulfatase E. We herein describe a male infant with chondrodysplasia punctata and stenosis and calcification of the entire trachea and main bronchi. To our knowledge, this is the first case of chondrodysplasia punctata reported in the English literature with such extensive airway manifestations.- - - - - - - - - - ranking = 2.8020315005288keywords = vitamin (Clic here for more details about this article) |
7/14. chondrodysplasia punctata: a boy with X-linked recessive chondrodysplasia punctata due to an inherited X-Y translocation with a current classification of these disorders.chondrodysplasia punctata (CDP) is a heterogeneous group of rare bone dysplasias characterized by punctate calcification of cartilage. The punctate calcifications are non-specific and have been seen in a wide variety of disorders including the zellweger syndrome, warfarin, dilantin, alcohol and rubella embryopathies, vitamin-K-epoxide-reductase deficiency, chromosome trisomies 18 and 21, the smith-lemli-opitz syndrome, prenatal infectious chondritis, hypothyroidism, and other rare disorders. We report on a boy with short stature, developmental delay, nasal hypoplasia, telebrachydactyly, hypoplastic genitalia, CDP, ichthyosis, hypoplastic genitalia, and a 46-X, der(X),t(X;Y)(p22.31;q11.21), Y karyotype. Genomic dna probe analysis was interpreted as showing that the translocation breakpoint was within the X-linked kallmann syndrome gene. We review a current classification of these disorders that includes 3 well-defined single gene disorders. These include an autosomal recessive rhizomelic type with early lethality, an X-linked dominant type with presumed male lethality, and an X-linked recessive type that has only been described as part of a contiguous gene deletion syndrome.- - - - - - - - - - ranking = 3.8020315005288keywords = vitamin, deficiency (Clic here for more details about this article) |
8/14. Very large peroxisomes in distinct peroxisomal disorders (rhizomelic chondrodysplasia punctata and acyl-coa oxidase deficiency): novel data.We report very large hepatic peroxisomes (d-circle greater than 1 micron) in a patient with rhizomelic chondrodysplasia punctata and a patient with acyl-coa oxidase deficiency. The effects of peroxisomal enlargement on the enzymatic activity are discussed. As increase in peroxisomal size is also reported in at least 12 other patients with peroxisomal disorders, we propose a relationship between the enlargement of the organelles and their functional deficiency.- - - - - - - - - - ranking = 6keywords = deficiency (Clic here for more details about this article) |
9/14. Deletion of the distal short arm of the x chromosome (Xp) in a patient with short stature, chondrodysplasia punctata, and X-linked ichthyosis due to steroid sulfatase deficiency.We observed a boy with short stature, chondrodysplasia punctata, ichthyosis, and a terminal deletion of Xp. Steroid sulfatase deficiency was demonstrated in the patient's fibroblasts. Molecular analysis showed a deletion of the entire steroid sulfatase gene. This case represents another example of a contiguous gene syndrome in which the co-deletion of adjacent genes on a chromosome is responsible for a complex phenotype.- - - - - - - - - - ranking = 5keywords = deficiency (Clic here for more details about this article) |
10/14. male infant with ichthyosis, kallmann syndrome, chondrodysplasia punctata, and an Xp chromosome deletion.We report on a male infant with X-linked ichthyosis, x-linked kallmann syndrome, and X-linked recessive chondrodysplasia punctata (CPXR). Chromosome analysis showed a terminal deletion with a breakpoint at Xp22.31, inherited maternally. This patient confirms the localization of XLI, XLK, and CPXR to this region of the x chromosome and represents an example of a "contiguous gene syndrome." A comparison of the manifestations of patients with CPXR, warfarin embryopathy, and vitamin K epoxide reductase deficiency shows a remarkable similarity. However, vitamin K epoxide reductase deficiency does not appear to be the cause of CPXR. We propose that CPXR may be due to a defect in a vitamin K-dependent bone protein such as vitamin K-dependent bone carboxylase, osteocalcin, or matrix Gla protein.- - - - - - - - - - ranking = 13.208126002115keywords = vitamin, deficiency (Clic here for more details about this article) |
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