scholarly journals Founder Mutation c.1516A>C in KLHL40 Is a Frequent Cause of Nemaline Myopathy With Hyponatremia in Ethnic Chinese

2019 ◽  
Vol 78 (9) ◽  
pp. 854-864 ◽  
Author(s):  
Han-Chih Hencher Lee ◽  
Shun Wong ◽  
Frank Ying-Kit Leung ◽  
Luen-Cheung Ho ◽  
Siu-Ki Timothy Chan ◽  
...  
Keyword(s):  
Hong Kong ◽  
Autosomal Recessive ◽  
Genetic Variant ◽  
Polymorphic Marker ◽  
Nemaline Myopathy ◽  
Ultrastructural Examination ◽  
Genetic Studies ◽  
Ethnic Chinese ◽  
Muscle Disorder ◽  
Nemaline Bodies

Abstract KLHL40-related nemaline myopathy is a severe autosomal recessive muscle disorder. The current study describes 4 cases of KLHL40-related nemaline myopathy in Hong Kong ethnic Chinese presenting within 3 years, which are confirmed with clinicopathologic features and genetic studies. The incidence is estimated to be at least 1 in 45 226 livebirths (at least 1 in 41 608 among ethnic Chinese livebirths) in Hong Kong. Hyponatremia appears to be another common feature in these patients. Salient histological features include nemaline bodies ranging from 200 to 500 nm in diameters on ultrastructural examination as well as negative KLHL40 immunohistochemistry; type II fiber predominance is obvious in 2 cases. We demonstrate the founder effect associated with genetic variant c.1516A>C (p.Thr506Pro) by polymorphic marker analysis, which revealed a 0.56–0.75-Mb or 0.41–0.78-cM shared haplotype encompassing the disease allele. The mutation is believed to have occurred around 412 generations ago or 6220 BCE, as estimated using DMLE+ and a formula described by Boehnke. We believe the founder variant might possibly underlie a sizable portion of nemaline myopathy in ethnic Chinese. Analysis of the KLHL40 gene may be considered as the first-tier testing of congenital myopathy in this ethnic group.

Abnormal actin binding of aberrant β-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy

2012 ◽  
Vol 442 (1) ◽  
pp. 231-239 ◽  
Author(s):  
Minttu Marttila ◽  
Elina Lemola ◽  
William Wallefeld ◽  
Massimiliano Memo ◽  
Kati Donner ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Nemaline Myopathy ◽  
Actin Binding ◽  
Muscle Fibres ◽  
Gene Encoding ◽  
Related Disorder ◽  
Structural Abnormalities ◽  
Muscle Disorder ◽  
Myosin Interaction ◽  
Nemaline Bodies

NM (nemaline myopathy) is a rare genetic muscle disorder defined on the basis of muscle weakness and the presence of structural abnormalities in the muscle fibres, i.e. nemaline bodies. The related disorder cap myopathy is defined by cap-like structures located peripherally in the muscle fibres. Both disorders may be caused by mutations in the TPM2 gene encoding β-Tm (tropomyosin). Tm controls muscle contraction by inhibiting actin–myosin interaction in a calcium-sensitive manner. In the present study, we have investigated the pathogenetic mechanisms underlying five disease-causing mutations in Tm. We show that four of the mutations cause changes in affinity for actin, which may cause muscle weakness in these patients, whereas two show defective Ca2+ activation of contractility. We have also mapped the amino acids altered by the mutation to regions important for actin binding and note that two of the mutations cause altered protein conformation, which could account for impaired actin affinity.

scholarly journals Molecular genetic verification of isolated mineralocorticoid deficiency due to aldosterone synthase deficiency

2009 ◽  
Vol 55 (1) ◽  
pp. 28-30
Author(s):  
N Yu Kalinchenko ◽  
N A Zubkova ◽  
A N Tyulpakov
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Adrenal Hyperplasia ◽  
Genetic Studies ◽  
Aldosterone Synthase ◽  
Salt Wasting ◽  
History Of ◽  
17 Hydroxyprogesterone ◽  
Aldosterone Synthase Deficiency

Isolated mineralocorticoid deficiency is a rare hereditary autosomal recessive disorder that is characterized by salt wasting and that has the severest manifestations in infants. This paper is the first in the Russian literature to describe cases of isolated aldosterone deficiency. In both cases, the patients were monitored and treated for misdiagnosed congenital adrenal hyperplasia; however, the permanently low level of 17-hydroxyprogesterone could put in doubt the diagnosis and suspect isolated mineralocorticoid deficiency, by keeping in mind a history of salt wasting. By using the presented cases as an example, the authors give an algorithm for the examination and differential diagnosis of this condition and other diseases that have the similar clinical picture. Aldosterone synthase deficiency in patients was verified by molecular genetic studies - there were mutations in the CYP112 gene.

scholarly journals Identification of a Large Deletion, Spanning Exons 4 to 11 of the Human Factor XIIIA Gene, in a Factor XIII-Deficient Family

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Rashida Anwar ◽  
Krzysztof J.A. Miloszewski ◽  
Alexander F. Markham
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Autosomal Recessive Disorder ◽  
Large Deletion ◽  
Factor Xiiia ◽  
Paternal Allele ◽  
Bleeding Tendency ◽  
Genetic Studies ◽  
Polymerase Chain

Inherited deficiency of factor XIIIA subunit (FXIIIA) is an autosomal recessive disorder that is characterized by a life-long bleeding tendency and complications in wound healing. Molecular genetic studies have shown the deficiency can be due to small sequence changes within the FXIIIA gene, such as point mutations or microdeletions. On molecular analysis of the FXIIIA gene in an FXIII-deficient patient, of United Kingdom origin, we identified a putative homozygous missense mutation, Arg408Gln. However, the father of this patient is homozygous normal for arginine at codon 408. Having proved paternity in this pedigree by microsatellite analysis, we examined the FXIIIA RNA of the patient by reverse transcriptase-polymerase chain reaction and found the paternal allele to lack exons 4 through 11 inclusive. Hence, a huge deletion extending from intron 3 to intron 11 and the Arg408Gln mutation are jointly responsible for FXIIIA deficiency in this family. This is the first finding of such a large deletion in the FXIIIA gene.

East Asian Pop Culture

2012 ◽  
Author(s):  
Chua Beng Huat
Keyword(s):  
Hong Kong ◽  
Chinese Language ◽  
East Asian ◽  
Pop Culture ◽  
Chinese Diaspora ◽  
Pop Music ◽  
Ethnic Chinese ◽  
Production Location ◽  
Cultural Boundaries ◽  
Production Distribution

Since the 1990s, there has been dense traffic of pop culture routinely crossing the national and cultural boundaries of East Asian countries of Japan, Korea, China, Taiwan, Hong Kong and Singapore. The unequal traffic is predominantly from Japan and Korea into ethnic-Chinese dominant locations, which has a historically long and well established production, distribution and exhibition network; Japan and Korea are primarily production-exporting nations, while China and Singapore as primarily importing-consumption ones, with Taiwan emerging as the production centre in Mandarin pop music and Hong Kong remaining as the primary production location of Chinese languages cinemas. Japanese and Korean pop culture are translated, dubbed or subtitled into a Chinese language in one of the ethnic-Chinese importing locations and then re-exported and circulated within the entire Chinese ‘diaspora’. The structures and processes that engender this transnational flow are the foundational to the emergence of an East Asian regional media cultural economy that increasingly see co-production of films and television dramas.

scholarly journals Hereditary C2 deficiency: Genetic studies and association with the HL-A system.

1975 ◽  
Vol 141 (6) ◽  
pp. 1464-1469 ◽  
Author(s):  
N K Day ◽  
R L'Esperance ◽  
R A Good ◽  
A F Michael ◽  
J A Hansen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Recessive Trait ◽  
Autosomal Recessive Trait ◽  
Systemic Lupus ◽  
Genetic Studies ◽  
Large Pedigree ◽  
Deficient Patient ◽  
Heterozygous Carriers ◽  
C2 Deficiency

Herediatary C2-deficiency has been shown to be transmitted asn an autosomal recessive characteristic. Recent evidence indicates that some genetic factors involved in the control of the complement (C) system in both man and mice are governed by genes localized within the major histocompatibility regionmthis study describes a large pedigree of the paternal family of a C2-deficient patient with systemic lupus erythematosusl It is shown that this condition is transmitted as an autosomal recessive trait, the heterozygous carriers having approximately half normal levels of C2. Furthermore, this trait was shown to be inherited in close linkage with an infrequent HL-A typw, 2,4A2. The maternal, C2-defective chromosome was shown to be transmitted by HL-AW10, W18 haplotypemthis same haplotype was described in a similar study by Fu et al. (6) to be associated with C2 deficiencymfinally, a third haplotype HL-A2,W18 carrying a defective C2 gene was demonstrated in a part of this pedigree.

Refined Localisation of the Genes for Nebulin and Titin on Chromosome 2q Allows the Assignment of Nebulin as a Candidate Gene for Autosomal Recessive Nemaline Myopathy

1997 ◽  
Vol 5 (4) ◽  
pp. 229-234 ◽  
Author(s):  
Katarina Pelin ◽  
Maaret Ridanpää ◽  
Kati Donner ◽  
Stephen Wilton ◽  
Janakan Krishnarajah ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Autosomal Recessive ◽  
Nemaline Myopathy

scholarly journals Mental health in Hong Kong: transition from hospital-based service to personalised care

2010 ◽  
Vol 7 (3) ◽  
pp. 62-64 ◽  
Author(s):  
Eric F. C. Cheung ◽  
Linda C. W. Lam ◽  
Se-fong Hung
Keyword(s):  
Mental Health ◽  
Hong Kong ◽  
Southern China ◽  
Central Intelligence Agency ◽  
Infant Mortality Rate ◽  
World Health ◽  
Intelligence Agency ◽  
Republic Of China ◽  
Ethnic Chinese ◽  
Health Organization

Hong Kong was a UK colony before 1997 but has since been a Special Administrative Region of the People's Republic of China. It is located in southern China and has an area of 1104 km2. Approximately 95% of Hong Kong's population is ethnic Chinese. Hong Kong is a developed capitalist economy, with a gross domestic product of US$301.6 billion (2009 estimate), of which about 5.5% is spent on healthcare and about 0.24% on mental health (World Health Organization, 2005). Despite the relatively low level of spending on healthcare, Hong Kong nevertheless has one of the longest life expectancies in the world (79.2 years for men; 84.8 years for women) and a very low infant mortality rate (2.93 per 1000 live births) (Central Intelligence Agency, 2010).

Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: novel sequence variants in ASPM gene

Neurogenetics ◽  
2006 ◽  
Vol 7 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Asma Gul ◽  
Muhammad Jawad Hassan ◽  
Saqib Mahmood ◽  
Wenje Chen ◽  
Safa Rahmani ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Sequence Variants ◽  
Primary Microcephaly ◽  
Genetic Studies ◽  
Autosomal Recessive Primary Microcephaly ◽  
Pakistani Families

scholarly journals Papillion-Lefèvre Syndrome: Periodontists’ Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Sunil Kumar Biraggari ◽  
K. Krishna Mohana Reddy ◽  
J. Sudhakar ◽  
Shiva Shankar Bugude ◽  
Rajesh Nichenametla ◽  
...  
Keyword(s):  
Gene Locus ◽  
Autosomal Recessive ◽  
Major Gene ◽  
Autosomal Recessive Inheritance ◽  
Signs And Symptoms ◽  
Loss Of Function ◽  
Gingival Inflammation ◽  
Deciduous Dentition ◽  
Genetic Studies ◽  
Present Case Report

Papillion-Lefèvre Syndrome is a very rare disorder of autosomal recessive inheritance distinguished by palmar plantar hyperkeratosis and early onset of periodontitis affecting the dentition. Genetic studies have identified a mutation in the major gene locus of chromosome 11q14 with loss of function. Cathepsin C gene is to be responsible for Papillion-Lefèvre Syndrome. The present case report describes a 13-year-old female, who visited the Department of Periodontology with the chief compliant of bleeding gums and loose teeth. She presented with the signs and symptoms of Papillion-Lefèvre Syndrome. The patient had premature shedding of her deciduous dentition. On clinical examination, extraorally, the patient presented with persistent thickening, flaking, and scaling of the skin of palms and soles. Her intraoral examination revealed gingival inflammation, abscess formation, and periodontal pockets. Her intraoral radiographs showed bone loss involving the central incisors and molars. The patient underwent periodontal therapy and is under maintenance.

Incidence of Plasma Cell Myeloma In Ethnic Chinese In British Columbia, a 30-Year Survey From 1975–2004

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2956-2956
Author(s):  
Vicky W. Chan ◽  
Kevin Song ◽  
Oscar Mang ◽  
Dennis Ip ◽  
Wing Y Au
Keyword(s):  
British Columbia ◽  
Hong Kong ◽  
Plasma Cell ◽  
Cancer Registry ◽  
Large Population ◽  
Incidence Rates ◽  
Plasma Cell Myeloma ◽  
Crude Incidence ◽  
Ethnic Chinese ◽  
Migrant Studies

Abstract Abstract 2956 Introduction: The incidence of plasma cell myeloma (PCM) in East Asian population is known to be 3–4 times lower than that in Caucasians. This may be due to genetic or environmental factors. Migrant studies may separate these factors to some extent by determining whether the disease incidence follows the parent or destination prevalence. British Columbia (BC) has a large population of Chinese migrants and therefore, it is an ideal population for migrant studies. Hong Kong (HK) is chosen as the comparison population because it has meticulous census data and a population-based cancer registry. Methods: Computerized records of all PCM cases diagnosed from 1975 to 2004 were retrieved from the British Columbia Cancer Agency (BCCA) and the Hong Kong Cancer Registry (HKCR). Cases with Chinese ethnicity in BC were identified by surname using a previously validated methodology and verified from electronic charts. Age distribution of HK, BC and BC Chinese populations for consecutive 5-secular year (yr.) periods were obtained from census departments from the respective governments. The crude incidence rates of PCM were calculated and 95% CI were determined using normal approximation of Poisson distribution. Projected PCM incidence rates in BC Chinese using HK and BC models were calculated and standard incidence ratios (SIR) estimated. Results: There was a steady increase in PCM from 1975 to 2004: from 42 to 159 cases/yr. in HK and from 86 to 207 cases/yr. in BC. This is likely due to population growth and aging. The proportion of population with age >65 grew from 5.4% to 11.2% in HK and from 9.7% to 13.2% in BC. From 1975–2004, a total of 106 cases of BC Chinese PCM were identified, increasing from 0.4 to 8 cases/yr. The BC Chinese population grew from 0.07 to 0.37 million, while the elderly subgroup (age >65) grew from 7.9% to 12.9%. Age specific mean 30-year crude incidence/100,000 person-years and 95% CI in the 3 cohorts were determined (Table 1). The standardized incidence ratio (SIR) of PCM in BC Chinese from 1975–2004 was 0.83 (95% CI 0.68–1.00) when compared to HK and 0.44 (0.36-0.53) when compared to the BC population. Cumulative SIRs of PCM in BC Chinese when compared to BC population remained low for incremental 5-year from 1975–2004 (Table 2). Conclusion: The incidence of PCM in ethnic Chinese in British Columbia is lower compared to the Caucasian counterparts, but similar to the incidence seen in HK. The trend is apparent in all age groups over 45 years old. This observation suggests a strong genetic predisposition in the development of PCM. Disclosures: No relevant conflicts of interest to declare.

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