Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene – KCNJ11:c1001G>7 (p.Gly334Val) – and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Tuberculosis in renal transplant patients: The experience of a single center in Medellín-Colombia, 2005-2013 / Tuberculose em pacientes transplantados renais: experiência de um único centro em Medellín-Colômbia, 2005-2013

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .

Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .

Long QT Syndrome: a Korean Single Center Study

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.

Association of the KCNJ11 Variant E23K with Type 2 Diabetes in Indo-Trinidadians / La Asociación de la Variante E23K de KCNJ11 con la Diabetes de Tipo 2 en Indo-Trinitenses

OBJECTIVE: To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians. METHODS: The coding and bordering intronexon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry, as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. Allele and haplotype frequency differences were calculated between cases and controls and linkage equilibrium was assessed across the KCNJ11 region. RESULTS: We identified novel missense mutations in both subject groups including A94P and R369C in a diabetic Indo-Trinidadian subject, S113G in a non-diabetic Indo-Trinidadian subject, and S118L in a diabetic Afro-Trinidadian subject. It is unknown if these mutations are pathogenic as other family members were not available for study. Additionally, the common variant E23K was associated with Type 2 diabetes in the Indo-Trinidadian group (OR = 1.797 [1.148-2.814], p = 0.0098). CONCLUSIONS: Rare variants in KCNJ11 are segregating in the Indo- and Afro-Trinidadian populations and further studies are needed to determine their contribution, if any, to the overall prevalence of diabetes in these groups. Common variants such as E23K may increase the risk in the Indo-Trinidadian population.

OBJETIVO: Examinar el efecto de la variación genética en KCNJ11 sobre el riesgo de la diabetes tipo 2 en trinitenses. MÉTODOS: Las regiones codificantes y las regiones de la frontera intrón-exón del gen KCNJ11 fueron secuenciadas en 168 sujetos diabéticos y 61 no diabéticos - históricamente de ascendencia del sur de la India - así como 66 sujetos diabéticos y 59 no diabéticos, de ascendencia africana. Se calcularon las diferencias de la frecuencia de los aleles y los haplotipos entre los casos y los controles, evaluándose asimismo el equilibrio de ligamiento de la región de KCNJ11. RESULTADOS: Se identificaron novedosas mutaciones de sentido erróneo en ambos grupos de sujetos, incluyendo A94P y R369C en un sujeto indo-trinitense diabético, y S118L en un sujeto afro-trinitense diabético. No se sabe si estas mutaciones son patogénicas ya que no se disponía de otros miembros de la familia para estudiar el caso. Además, la variante E23K estaba asociada con la diabetes tipo 2 en el grupo indo-trinitense (OR = 1.797 (1.148-2.814), p = 0.0098). CONCLUSIONES: Variantes raras en el KCNJ11 se están segregando en las poblaciones indo - y afro-trinitenses, y se requieren estudios ulteriores para determinar si de algún modo contribuyen a la prevalencia general de la diabetes en estos grupos. Las variantes comunes como la E23K pueden aumentar el riesgo en la población de indo-trinitense.

Long-term response to sulfonylurea in a patient with diabetes due to mutation in the KCNJ11 gene / Resposta a longo prazo com sulfonilureia em um paciente com diabetes associado à mutação no gene KCNJ11

OBJECTIVE: To report the long-term (30-month) effect of the switch from insulin to sulfonylurea in a patient carrying the p.G53D (c.158G>A) mutation in KCNJ11 gene. SUBJECT AND METHOD: A 29-year-old male patient was diagnosed with diabetes in the third month of life and after identification of a heterozygous p.G53D mutation in the KCNJ11 gene, the therapy was switched from insulin to sulfonylurea. RESULTS: Long-term follow-up (30 months) showed that good metabolic control was maintained (HbA1c: 6.6 percent) and the glibenclamide dose could be reduced. CONCLUSION: Long-term therapy with sulfonylureas in patients with neonatal diabetes due to mutation in the KCNJ11 gene is safe and promotes sustained improvement of glycemic control.

OBJETIVO: Reportar o efeito a longo prazo (30 meses) da substituição de insulina por sulfonilureia em um paciente com a mutação p.G53D (c.158G>A) no gene KCNJ11. SUJEITO E MÉTODO: Paciente do sexo masculino, atualmente com 29 anos de idade, foi diagnosticado com diabetes melito no terceiro mês de vida e, após identificação da mutação p.G53D (c.158G>A) em heterozigose no gene KCNJ11, a terapia foi substituída de insulina para sulfonilureia. RESULTADOS: Seguimento a longo prazo (30 meses) mostrou que o bom controle metabólico foi mantido (HbA1c: 6,6 por cento) e a dose de glibenclamida pode ser reduzida. CONCLUSÃO: A terapia com sulfonilureia a longo prazo em pacientes com diabetes neonatal decorrente de mutações no gene KCNJ11 é segura e promove uma melhora persistente no controle metabólico.

Persistent hyperinsulinemic hypoglycemia of infancy due to homozygous KCNJ11 (T294M) mutation.

Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in infancy. While most of the cases are sporadic more than 100 mutations have been reported in the familial type. The authors report a case of familial hyperinsulinemic hypoglycemia with homozygous T294M mutation of the KCNJ11 gene, which responded to diazoxide therapy.

KCNJ11 activating mutation in an indian family with remitting and relapsing diabetes.

Objective. To identify the genetic cause of transient neonatal diabetes mellitus in three siblings from an Indian family. Methods. Case reports with clinical and molecular evaluation of an activating mutation in the KCNJ11 gene are presented. We describe an Indian family with two asymptomatic parents with 3 children presenting with hyperglycemia at 6, 1.5 and 1 month of age respectively. Blood glucose levels at presentation were 22.2, 18.3 and 20 mmol/L and the diabetes remitted in all three children by 5 years of age. None of the affected siblings had dysmorphism or neurological abnormalities. Diabetes relapsed in the oldest sibling at 9.4 years of age and she is now euglycemic on 1mg/Kg of Glibenclamide twice a day. Results. A novel heterozygous missense mutation (G53V) in the KCNJ11 gene was identified in all 3 affected children and the father. Conclusions. The report suggests that screening for KCNJ11 mutations is appropriate in patients diagnosed with neonatal diabetes as it provides valuable information concerning possible course of the disease and choice of treatment.

Successful transfer from insulin to oral sulfonylurea in a 3-year-old girl with a mutation in the KCNJ11 gene

Neonatal diabetes mellitus is considered a rare disease that is diagnosed in the first six months of life, and can be either transient or permanent. Recent advances in molecular genetics have shown that activating mutations in KCNJ11 [the gene that encodes for the Kir6.2 subunit of the K[ATP] potassium channel of the pancreatic beta-cell] is a common cause of permanent neonatal diabetes mellitus. Patients with mutations in this gene may respond to oral sulfonyureas. We describe a 3-year-old girl with permanent neonatal diabetes mellitus with a mutation in the KCNJ11 gene [R201H], who was successfully transferred from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control. This is the first successful switch from insulin to oral sulfonylurea in a patient with R201H mutation, in the Arabian Gulf

Transient neonatal diabetes due to activating mutation in the ABCC8 gene encoding SUR1.

We report a 2 month male child presenting with diabetic ketoacidosis (DKA) and seizures treated with intravenous fluids and intravenous insulin infusion till the ketoacidosis was reversed, thereafter responding well to sulphonylureas and at age of 13 months going into complete remission. At age of 11 mo developmental delay in the form of negative neck holding and inability to sit without support was seen. The child is 3 yr of age now ,euglycemic without any insulin or oral hypoglycemic agents but has severe developmental delay. Genetic analysis was negative for mutations of KCNJ11, 6q24, Glucokinase and IPF-1 genes. A mutation R1183W was found in the ABCC8 gene encoding SUR1, which was the cause of neonatal diabetes in this case.

Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene / Falha de resposta à glibenclamida em criança brasileira com diabetes melito neonatal permanente e síndrome DEND devido a mutação C166Y no gene KCNJ11 (Kir6.2)

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.

As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida.

Diabetes melito neonatal: [revisão] / Neonatal diabetes mellitus: [review]

O diabetes neonatal (DN) é uma condição rara caracterizada por hiperglicemia, que necessita de tratamento com insulina, diagnosticado nos primeiros meses de vida. Clinicamente pode ser classificado em DN transitório quando ocorre remissão da doença em poucos meses, podendo haver recorrência posterior; ou permanente quando, como o nome indica, não ocorre remissão. Ambas as condições são geneticamente heterogêneas; entretanto a maioria dos casos de DN transitório é decorrente de anormalidades da região de imprinted no cromossomo 6q24. Mutações ativadoras em heterozigose no gene KCNJ11, que codifica a subunidade Kir6.2 do canal de potássio ATP-sensível, são a causa mais comum de DN permanente. No presente artigo, discutimos as características clínicas do DN, os mecanismos moleculares envolvidos e suas implicações terapêuticas.

Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.

Changes in Inward Rectifier K+ Channels in Hepatic Stellate Cells During Primary Culture

PURPOSE: This study examined the expression and function of inward rectifier K+ channels in cultured rat hepatic stellate cells (HSC). MATERIALS AND METHODS: The expression of inward rectifier K+ channels was measured using real-time RT-PCR, and electrophysiological properties were determined using the gramicidin-perforated patch-clamp technique. RESULTS: The dominant inward rectifier K+ channel subtypes were K(ir)2.1 and K(ir)6.1. These dominant K+ channel subtypes decreased significantly during the primary culture throughout activation process. HSC can be classified into two subgroups: one with an inward-rectifying K+ current (type 1) and the other without (type 2). The inward current was blocked by Ba2+ (100micrometer) and enhanced by high K+ (140mM), more prominently in type 1 HSC. There was a correlation between the amplitude of the Ba2+-sensitive current and the membrane potential. In addition, Ba2+ (300micrometer) depolarized the membrane potential. After the culture period, the amplitude of the inward current decreased and the membrane potential became depolarized. CONCLUSION: HSC express inward rectifier K+ channels, which physiologically regulate membrane potential and decrease during the activation process. These results will potentially help determine properties of the inward rectifier K+ channels in HSC as well as their roles in the activation process.

Permanent neonatal diabetes due to KCNJ11 gene mutation.

Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of diabetes within the first six months of life and insulin dependence life long. It has been recently discovered that mutation in KCNJ11 gene encoding Kir6.2, the pore forming subunit of ATP sensitive potassium channel (K ATP) is the most common cause and such patients may respond better to oral sulphonylurea drugs than insulin. Here is a rare case of permanent neonatal diabetes due to R20IC mutation in KCNJ11 gene.

Sulfonylurea Therapy in Two Korean Patients with Insulin-treated Neonatal Diabetes due to Heterozygous Mutations of the KCNJ11 Gene Encoding Kir6.2

Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K(+) channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.

Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities / Síndrome de Andersen: uma associação de paralisia periódica com arritmia cardíaca e alterações dismórficas

Andersen syndrome (AS) is a rare disease characterized by the presence of periodic paralysis (PP), cardiac arrhythmia and dysmorphic abnormalities. We report herein the first Brazilian patient presenting AS who also had obesity, obstructive sleep apnea (OSA) and daytime sleepiness. Clinical and genetic evaluation of six family members demonstrated that four had dysmorphic abnormalities but none had PP or cardiac arrhythmia. Sequencing of KCNJ2 revealed the R218W mutation in the index patient and her 6-year-old daughter, who presented dysmorphic abnormalities (micrognathia, clinodactyly of fourth and fifth fingers, short stature) and OSA. Three relatives had clinodactyly as the only manifestation but the R218W mutation was absent, suggesting that this characteristic may be influenced by another gene. OSA accompanied by dysmorphic features may be related to AS.

A síndrome de Andersen (SA) é doença rara caracterizada pela presença de paralisia periódica (PP), arritmia cardíaca e anormalidades dismórficas. Relatamos o primeiro paciente brasileiro apresentando SA, e que também apresenta obesidade e apnéia obstrutiva do sono (AOS). Avaliações clínica e genética de seis familiares demonstraram que quatro apresentavam alterações dismórficas mas nenhum tinha PP ou arritmia cardíaca. O sequenciamento do gene KCNJ2 revelou a mutação R218W no paciente índex e sua filha de 6 anos, que apresentava alterações dismórficas (micrognatia, clinodactilia do quarto e quinto dedos, baixa estatura) e AOS. Três familiares tinham clinodactilia como única manifestação mas a mutação R218W estava ausente, sugerindo que esta característica seja influenciada por outro gene. A AOS associada a alterações dismórficas pode estar relacionada à SA.

Cloning of a pore-forming subunit of ATP-sensitive potassium channel from Clonorchis sinensis

A complete cDNA sequence encoding a pore-forming subunit (Kir6.2) of ATP-senstive potassium channel in the adult worm, Clonorchis sinensis, termed CsKir6.2, was isolated from an adult cDNA library. The cDNA contained a single open-reading frame of 333 amino acids, which has a structural motif (a GFG-motif) of the putative pore-forming loop of the Kir6.2. Peculiarly, the CsKir6.2 shows a lack-sequence structure, which deleted 57 amino acids were deleted from its N-terminus. The predicted amino acid sequence revealed a highly conserved sequence as other known other Kir6.2 subunits. The mRNA was weekly expressed in the adult worm.