OBJECTIVETo identify the genetic defect in a four-generation pedigree with X-linked recessive spondyloepiphyseal dysplasia tarda (SEDT) from Southwest China.

METHODSLinkage analysis with one panel of fluorescently labeled microsatellite markers on chromosome X and mutation screening of SEDL gene by direct sequencing were performed.

RESULTSLinkage between SEDT and Xp22.2-Xp23.1 was established with maximum LOD score of 3.82 (theta = 0) between DXS987 and DXS8051. Upon sequence analysis, a point mutation within exon 4 of the SEDL gene (c.239A to G) was found which resulted in substitution of histidine with arginine at codon 80 (His80Arg).

CONCLUSIONA novel missense mutation (H80R) was identified for SEDL gene in the large Chinese SEDT pedigree.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; Female ; Genetic Diseases, X-Linked ; genetics ; pathology ; Genetic Linkage ; genetics ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Mutation, Missense ; genetics ; Osteochondrodysplasias ; genetics ; pathology ; Pedigree ; Transcription Factors ; genetics

No abstract available.
5-Aminolevulinate Synthetase/chemistry/*genetics ; Adult ; Anemia, Sideroblastic/*genetics/pathology ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Genetic Diseases, X-Linked/*genetics/pathology ; Hemizygote ; Humans ; Male ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Republic of Korea

PURPOSE: X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease caused by a mutation in the Bruton tyrosine kinase (BTK) gene resulting in defective B cell differentiation. Because it is a relatively rare disorder, it is difficult for clinicians to have a comprehensive understanding of XLA due to a lack of exposure to the disease. Clinical presentations of patients with XLA were analyzed and discussed to improve care plans. MATERIALS AND METHODS: During a 20 year period, from January 1987 to June 2006, a total of 19 patients were diagnosed as XLA in the Department of Pediatrics at Severance Hospital, Seoul, Korea. A retrospective analysis of the clinical presentations of those patients was performed. RESULTS: The mean age of the XLA patients included in the study was 4.89 years, with a range of 6 months to 13 years. Twelve patients were diagnosed before age 5, while the other 7 patients were diagnosed after age 5. Recurrent infections observed in the patients included pneumonia, acute otitis media, septic arthritis, skin infection, sepsis, sinusitis, acute gastroenteritis, cervical lymphadenitis, epididymitis, meningitis, osteomyelitis, urinary tract infection and encephalitis. Frequency of admissions was variable from 0 to 12 times, depending on the time at which immunoglobulin therapy was started. Six cases had family histories positive for XLA. BTK gene mutations were found in 8 cases. CONCLUSION: The overall prognosis of XLA is good as long as patients are diagnosed and treated early with regular intra venous gamma globulin therapy before the sequelae of recurrent infections appear.
Adolescent ; Agammaglobulinemia/complications/*diagnosis/drug therapy/genetics ; Child ; Child, Preschool ; Genetic Diseases, X-Linked/enzymology/genetics/pathology ; *Hospitals ; Humans ; Infant ; Male ; Protein-Tyrosine Kinases/genetics/metabolism ; Retrospective Studies ; Time Factors

OBJECTIVETo further investigate the genetic basis of hereditary X-linked spondyloepiphyseal dysplasia tarda (SEDL) and provide useful information for the prevention and treatment of the disease.

METHODSRT-PCR and cDNA sequencing were used to test mRNA expression of SEDL gene in a patient with 13 bp deletion of SEDL gene involving the acceptor splice site of intron 5.

RESULTSOf two different sizes of mRNA products identified in the patient, the 393 bp product was created due to the activation of cryptic splice site within exon 6; the 433 bp product was completely consistent with the part of genomic sequence on chromosome 8.

CONCLUSIONThe intragenic deletion that occurred in the acceptor splice site of the 3'region of intron 5 and the 5' coding region of exon 6 results in the activation of a cryptic splice site within exon 6, which causes 47 bp deletion of the resulting mRNA followed by a frameshift that would add two missense amino acids and then be followed by a termination codon (D109-S123del; S124fsX126). In addition, the mutation may activate the transcription of pseudogene SEDLP2 on chromosome 8 to partly complement the function of SEDL protein.

Adolescent ; Base Sequence ; Chromosomes, Human, Pair 8 ; genetics ; DNA Mutational Analysis ; Exons ; genetics ; Genetic Diseases, X-Linked ; genetics ; pathology ; Humans ; Introns ; genetics ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Osteochondrodysplasias ; genetics ; pathology ; RNA Splice Sites ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors ; genetics

OBJECTIVETo investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital(AHC).

METHODSClinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database.

RESULTSA novel hemizygous frameshift mutation (428delG) in exon 1 of the DAX-1 gene was found in both patients (the index case and his cousin). Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family.

CONCLUSIONThe result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in the DAX-1 gene, and the same mutation can give rise to variable phenotypes.

Adolescent ; Adrenal Hyperplasia, Congenital ; genetics ; pathology ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; DAX-1 Orphan Nuclear Receptor ; DNA-Binding Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; pathology ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Receptors, Retinoic Acid ; genetics ; Repressor Proteins ; genetics ; Sequence Analysis, DNA