X-linked recessive chondrodysplasia punctata due to a new point mutation of the ARSE gene
Department of Pediatrics, Federico II University, Naples, Italy.American Journal of Medical Genetics (Impact Factor: 3.23). 01/1998; 73(2):139-43. DOI: 10.1002/(SICI)1096-8628(19971212)73:2<139::AID-AJMG7>3.0.CO;2-P
Chondrodysplasia punctata (CP) is a heterogeneous group of bone dysplasias that are characterized by abnormal calcium deposition in areas of enchondral bone formation. The existence of an X-linked recessive form of chondrodysplasia punctata (CDPX) has been recognized in patients who are nullisomic for the Xp22.3 region, presenting with complex phenotypes. The gene of CDPX has been identified recently, and five point mutations of the gene, named ARSE, have been described. Here, we report on the clinical and molecular characterization of a patient with CDPX. The patient presented at birth with cranial and facial anomalies and short stature; an x-ray skeletal survey showed punctate calcifications and striking hand and foot abnormalities. Single strand conformation polymorphism (SSCP) and sequence analysis of the patient's DNA allowed the identification of a new mutation of the ARSE gene; this mutation causes an amino acid substitution from cysteine to tyrosine at position 492 of the ARSE predicted protein product. The clinical description of patients with CDPX due to known mutation of the ARSE is of interest for the precise delineation of the clinical spectrum of the disease.
[Show abstract] [Hide abstract]
- "Other systems involved: intracranial hemorrhage, hydrocephaly 2 , supendymal cysts 2 , basal ganglia ischemia 1 , hypogammaglobulinemia 2 , hypothyroidism 2 , joint contractures, joint laxity 2 . b This article, P1–P7 [Franco et al., 1995; Parenti et al., 1997; Sheffield et al., 1998; Dahl et al., 1999, (follow-up on patient reported by Franco); Brunetti-Pierri et al., 2003; Wolpoe et al., 2004 ( patient P2 in this manuscript ) ; Garnier et al. , 2006 ] . and the absence of the allele in a population of normal controls . "
ABSTRACT: X-linked Recessive Chondrodysplasia Punctata (CDPX1) is due to a defect in arylsulfatase E (ARSE), located on Xp22.3. Neither the substrate nor function of the encoded warfarin-sensitive arylsulfatase has been identified and molecular analysis remains the only confirmatory diagnostic test. Nevertheless, the majority of patients evaluated have not had identifiable mutations in ARSE, and thus far 23 patients have been reported. The major clinical features in these patients are also present in a group now recognized as phenocopies, due to vitamin K deficiency in early gestation or maternal autoimmune disease. We evaluated the ARSE gene in 11 patients who met clinical criteria for CDPX1. We amplified all exons and intronic flanking sequence from each patient, and investigated suspected deletions or rearrangements by southern analysis. We identified mutations in seven individuals. Of the remainder, three had maternal conditions that further expand the phenocopy group. Thus, this group might represent a proportion of the mutation-negative patients in previous studies. We extracted clinical information from all prior reports over the past decade and show that there are few distinguishing features on examination between these two groups of patients. This study supports heterogeneity for CDPX1-like phenotypes and sorting these out will help to define the biological pathway and genetic contributors.American Journal of Medical Genetics Part A 04/2008; 146A(8):997-1008. DOI:10.1002/ajmg.a.32159 · 2.16 Impact Factor
[Show abstract] [Hide abstract]
- "Single nucleotide changes that produce the amino acid substitutions R12S, R111P, G137V, G245R, and C492Y were identified in patients affected with CDPX (Franco et al. 1995; Parenti et al., 1997). To investigate the effect of these missense mutations, the nucleotide changes leading to these amino acid substitutions were introduced into the wild-type ARSE expression vector by site-directed mutagenesis. "
ABSTRACT: X-linked chondrodysplasia punctata (CDPX) is a congenital disorder characterized by abnormalities in cartilage and bone development. Mutations leading to amino acid substitutions were identified recently in CDPX patients, in the coding region of the arylsulfatase E (ARSE) gene, a novel member of the sulfatase gene family. Transfection of the ARSE full-length cDNA, in Cos7 cells, allowed us to establish that its protein product is a 60-kD precursor, which is subject to N-glycosylation, to give a mature 68-kD form that, unique among sulfatases, is localized to the Golgi apparatus. Five missense mutations found in CDPX patients were introduced into wild-type ARSE cDNA by site-directed mutagenesis. These mutants were transfected into Cos7 cells, and the arylsulfatase activity and biochemical properties were determined, to study the effect of these substitutions on the ARSE protein. One of the mutants behaves as the wild-type protein. All four of the other mutations resulted in a complete lack of arylsulfatase activity, although the substitutions do not appear to affect the stability and subcellular localization of the protein. The loss of activity due to these mutations confirms their involvement in the clinical phenotype and points to the importance of these residues in the correct folding of a catalytically active ARSE enzyme.The American Journal of Human Genetics 04/1998; 62(3):562-72. DOI:10.1086/301746 · 10.93 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Sixteen males and two females with symmetrical (mild) type of chondrodysplasia punctata were tested for mutations in the X chromosome located arylsulphatase D and E genes. We identified one nonsense and two missense mutations in the arylsulphatase E gene in three males. No mutations were detected in the arylsulphatase D gene. Family studies showed segregation of the mutant genes establishing X linked inheritance for these families. Asymptomatic females and males were found in these studies. The clinical presentation varies not only between unrelated affected males, but also between affected males within the same family. We also conclude that clinical diagnosis of chondrodysplasia punctata in adults can be difficult. Finally, our results indicate that brachytelephalangy is not necessarily a feature of X linked symmetrical chondrodysplasia punctata.Journal of Medical Genetics 01/1999; 35(12):1004-8. DOI:10.1136/jmg.35.12.1004 · 6.34 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.