• Journal of Audiology & Otology
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• 제23권1호
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• pp.20-26
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• 2019

Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. Subjects and Methods: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). Results: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.

• 대한청각학회지
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• 제23권1호
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• pp.20-26
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• 2019

Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. Subjects and Methods: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). Results: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.

• 생명과학회지
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• 제31권5호
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• pp.453-463
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• 2021

청력 장애(hearing loss)는 임상적 및 유전적으로 상당히 이질적인 질병들의 그룹으로, 일반적으로 증후군 유형(syndromic type)과 비증후군 유형(non-syndromic type)으로 구분된다. 상염색체 열성의 청력 장애 환자가 다른 나라들에 비해 파키스탄에서는 상대적으로 흔하게 관찰되는데, 그 원인으로는 빈번한 근친 결혼의 문화가 일부 관여할 것으로 여겨진다. 본 연구는 상염색체 열성의 청력 장애 환자가 있는 두 파키스탄의 근친 가계를 대상으로 전장 엑솜 서열분석(whole exome sequencing)을 실시하여 유전적 원인을 규명하기 위해 수행되었다. 환자의 유전체 분석 결과, 우리는 언어 습득전 발병(prelingual onset)의 청력 장애 가족으로부터 MYO7A 유전자에서 병원성으로 판단되는 동형접합성 돌연변이인 p.Leu326Gln을 분리하였으며, 조기 발병의 청력 장애와 동시에 근위축(muscular atrophy)을 나타내는 환자 가족에서는 병원성이 확실하지 않는 두 변이(variants of uncertain significance)를 GPR98 유전자(p.Val3094Ile)와 PLA2G6 유전자 (p.Asp56Gly)에서 각각 분리하였다. MYO7A 및 PLA2G6 유전자의 missense 돌연변이는 고도로 보존된 단백질 부위에 위치했으며, 인실리코 분석(in silico analysis)에서도 병원성을 예측하였다. 그러나, GPR98 유전자의 돌연변이는 보존성이 다소 낮은 부위에 위치하였으며, 대부분의 인실리코 분석도 비병원성으로 예측했다. 동형접합성 매핑(homozygosity mapping)을 실시하였을 때, 각 가계에서 분리된 동형접합성 돌연변이의 두 대립유전자가 모두 단일 기원에서 유래한 것으로 예측되었는데, 이것은 근친 결혼에 기인한 것으로 판단된다. 본 연구는 파키스탄의 상염색체 열성 청력 장애 환자들의 정확한 분자진단 및 치료에 도움을 줄 수 있을 것으로 기대된다.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 춘계학술발표대회
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• pp.48-48
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• 2001

A new neurological mutant has been found in the ICR outbred strain mouse. Affected mice display profound deafness and a head-tossing and bidirectional circling behavior, showing an autosomal recessive mode of inheritance. It was, therefore, named cir/Kr with the gene symbol cir. The auditory tests identified clearly the hearing loss of the cir mice when compared to wild type mice. Pathological studies confirmed the developmental defects in the middle ear, cochlea, cochlear nerve, and semicircular canal areas, which were correlated to the abnormal behavior observed in the cir mice. Thus, cir mice may be useful as a model for studying inner ear abnormalities and deafness. We have constructed a genetic linkage map by positioning 14 microsatellite markers across the (cir) region and intraspecific backcross between cir and C57BL/6J mice. The cir mouse harbors an autosomal recessive mutation on mouse chromosome 9. The cir gene was mapped to a region between D9Mit116 and D9Mit38 Estimated distances between cir and D9Mit116, and between cir and D9Mit38 are 0.7 and 0.2 cM, respectively. The gene in order was defines : centromere-D9Mit182-D9Mit51/D9Mit79/D9Mit310-D9Mit212/D9Mit184-D9Mit116-cir-D9Mit38-D9Mit20-D9Mit243-D9Mit16-D9Mit55/D9Mit125-D9Mit281. The mouse map location of the cir locus appears to be in a region homologous to human 3q21. Our present date suggest that the nearest flanking marker D9Mit38 provides a useful anchor for the isolation of the cir gene in a yeast artificial chromosome contig.

• Journal of Genetic Medicine
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• 제11권2호
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• pp.63-68
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• 2014

Purpose: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. Materials and Methods: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. Results: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. Conclusion: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.

• Childhood Kidney Diseases
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• 제26권1호
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• pp.31-39
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• 2022

Alport syndrome (AS) is a progressive hereditary nephritis that is often accompanied by sensorineural hearing loss and ocular abnormalities. It is inherited in three modes of X-linked AS (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ARAS and ADAS are caused by those in COL4A3 or COL4A4. There is currently no curative treatment for AS; however, angiotensin-converting enzyme inhibitors (ACEi) can improve the outcome of AS. In the past decade, multiple studies have shown that early intervention with ACEi upon isolated microscopic hematuria or microalbuminuria could delay disease progression, and early diagnosis is crucial for early treatment. Therefore, a new classification of AS based on molecular diagnoses has been proposed, including the paradigm shift of re-classifying female "carriers" to "patients" and "thin basement membrane nephropathy" to "ADAS." In addition, with the detection of COL4A mutations in some patients with biopsy-confirmed IgA nephropathy, focal segmental glomerulosclerosis, and chronic kidney disease of unknown origin, it is suggested that the phenotype of AS should be expanded. In this review, we highlight the landmark studies and guidelines published over the past decade and introduce strategies for early diagnosis and treatment to improve the outcomes of AS.

• 대한소아치과학회지
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• 제26권4호
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• pp.636-643
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• 1999

유전적인 외배엽 이형성증에 의해 무치증 혹은 부분적 무치증을 가진 환아들은 치조골 발육의 부족으로 나타난 감소된 수직고경으로 인해 어린 나이에서 노인과 같은 안모를 가지게 된다. 이에 어린이들은 또래의 어린이들과 잘 어울릴 수 없게 되고 소외감과 정서적 위축감을 느끼게 된다. 수직고경을 고려한 보철적 치료를 통해 적절한 기능과 심미적인 개선을 이룰 수 있도록 도와주는 것이 치과의사의 중요한 역할이라 하겠다. 이에 저자는 경희대학교 치과대학 부속치과병원 소아치과에 내원한 부분적 무치증을 동반한 외배엽 이형성증을 가진 환아에서 치과치료를 통한 심미적, 기능적 결함을 개전하면서 다음과 같은 결론을 얻었기에 보고하는 바이다. 1. 맹출 영구치 위에 클래스프를 위치시켜 의치유지력에 도움을 주었으며 상하악 피개의치의 장착으로 교합고경을 회복하여 저작, 발음, 심미적인 개선이 이루어졌다. 2. 피개의치의 이용으로 교합평면의 설정과 의치의 유지와 안정을 도모하였고, 맹출한 치아를 보존하고 남아있는 치조골의 폭과 높이를 유지할 수 있었다. 3. 치료를 통해 환아는 외모에 자신감을 가지고 치과환경에 익숙해져 긍정적인 태도를 가지게 되었다. 4. 주기적인 내원을 통한 영구치 상태와 성장, 발육동안의 의치의 관찰로 의치의 이장, 재제작이 요구된다.