• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.7-14
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• 2021

Purpose: Pseudohypoparathyroidism (PHP) is caused by genetic and epigenetic alteration in the GNAS locus, and characterized by the resistance to multiple hormones and the Albright's hereditary osteodystrophy (AHO) phenotype. This study investigated the phenotypic characteristics and molecular features of PHP. Methods: Eight patients who diagnosed as PHP were enrolled at Pusan National University Children's hospital and clinical features, biochemical and genetic findings were retrospectively reviewed. Results: Of a total of 8 patients, 5 were diagnosed with PHP1a, and 3 were diagnosed with PHP1b. Patients with PHP1a had three different mutations in the GNAS gene, and patients with PHPIb had imprinting defect in differentially methylated regions (DMRs) of the GNAS locus. Two novel GNAS variants were identified in patients with PHP1a, including c.313-2A>T and c.1094G>A. All patients with PHP1a displayed AHO features; short stature (80%), brachydactyly (80%), a round face (80%), obesity (40%), heterotopic ossification (60%), and intellectual disability (60%), whereas only one patient (33.3%) with PHP1b showed AHO feature such as a round face. When phenotypic features between PHP1a and PHP1b patients were compared, patients with PHP1b showed a tendency of higher current height standard deviation scores (SDS) compared to patients with PHP1a, (-3.2±2.1 vs.-1.1±0.8; P=0.06) Conclusions: This study summarizes the phenotypic and genetic features of the PHP patients. Although we found considerable clinical overlap between PHP1a and PHP1b, further long-term follow-up is needed to evaluate the growth and development of children with PHP, as well as the effects of end-organ resistances to endocrine hormones.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.298-305
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• 2005

Background : Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. Methods : Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. Results : The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLADRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index >45) than in the controls (p<0.05). Conclusion : This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS.