CADASIL caused by mutation of NOTCH3 gene c.697T>A: a report on a Chinese family / 国际脑血管病杂志

Objective:To report the clinical features, imaging findings and gene mutation features of a Chinese family with cerebral autosomal dominant arteriopathy with subcritical infarcts and leukoencephalopathy (CADASIL).Methods:We summarized the clinical and imaging features of a CADASIL family confirmed by gene sequencing. NOTCH3 gene sequencing was conducted for the proband, and the structure of the protein encoded by the mutant gene was predicted. Results:The patients in this family mainly presented with recurrent lacunar infarction and hypertension, without headache and emotional disorders such as anxiety or depression. Head MRI of the proband showed multiple lacunar infarctions and extensive white matter degeneration. Susceptibility-weighted imaging showed multiple small intracranial hemorrhages. The analysis of NOTCH3 gene showed that the proband had c.697T>A mutation. The 3D structure prediction of the protein encoded by this mutation locus showed that this locus could lead to the conversion of cysteine to serine at the 233rd position. Conclusions:The patients of this CADASIL family have a c.697T>A mutation of NOTCH3 gene. This mutation may cause the change of amino acid in the structure of the wild type Notch3 protein, which may lead to increased formation of β-folding structures in the surrounding region, thus changing the structure and function of protein and causing disease.

Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome type Ⅲ / 中华围产医学杂志

This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.

A neonate with Smith-Lemli-Opitz syndrome caused by DHCR7 gene compound heterozygous variations / 中华围产医学杂志

This article reported a male neonate with Smith-Lemli-Opitz syndrome (SLOS) caused by DHCR7 gene compound heterozygous variations. The patient presented with multiple malformations and feeding difficulties after birth and was transferred to the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) from a local hospital eight days later. Physical examination found general scleredema, scalp defects, short penis, urinary tract malformation, bilateral syndactyly of the second and third toes, and low serum cholesterol. Whole-exome and Sanger sequencing indicated a compound heterozygous mutation in the DHCR7 gene, c.852C>A(p.F284L), and a de novo mutation of c.820_825del(p.N274_V275del). SLOS is rare in the Asian populations and prone to missed diagnosis and misdiagnosis with difficulty in clinical management. The possibility of SLOS should be considered for newborns with multiple malformations and low serum cholesterol.

Assessing cardiovascular risk in ATM heterozygotes / Avaliação do risco cardiovascular de ATM heterozigotos

Summary Objective: To evaluate the carotid intima-media complex (CIMC) thickness and lipid metabolism biomarkers associated with cardiovascular risk (CR) in parents of patients with ataxia-telangiectasia and verify an association with gender. Method: A cross-sectional and controlled study with 29 ATM heterozygotes and 14 healthy controls. Biochemical tests and CIMC thickness measurement were performed. Results: The mean CIMC measurement in heterozygous ATM was 0.72 ± 0.1 mm (minimum: 0.5 mm and maximum: 1.0 mm). Noticed high percentage of amounts above 75 percentile compared to the population referential (16 [76.2%]), without any significant statistical differences between the female and the male gender (11/15 [73.3%] vs. 5/6 [83.3%]; p=0.550). The comparison between heterozygous and controls, stratified by gender, showed that in heterozygous ATMs, women had higher concentrations of HDL-c compared to men, as well as higher values of hs-CRP in relation to the control women. In heterozygous ATMs, stratified by gender, the correlation between HDL-c and hs-CRP was inversely proportional and stronger among women, with a tendency to statistical significance. Conclusion: Heterozygous ATMs did not differ from controls in relation to the biomarkers studied related to CR. However, most of them presented increased CIMC, independent predictor of death, risk for myocardial infarction and stroke, compared to the referential for the same age group. This finding suggests CR in the heterozygous ATM and shows to the need to monitor CIMC thickness and nutritional orientations.

Resumo Objetivo: Avaliar a espessura do complexo médio-intimal da carótida (CMIC) e os biomarcadores do metabolismo lipídico associados ao risco cardiovascular (RC) em pais de pacientes com ataxia-telangiectasia (AT) e verificar associação com gênero. Método: Estudo transversal prospectivo e controlado com 29 ATM heterozigotos e 14 controles saudáveis. Foram realizados exames bioquímicos e a espessura do CMIC por ultrassonografia. Resultados: A média da medida do CMIC nos ATM heterozigotos foi de 0,72± 0,1 mm (mínimo: 0,5 mm e máximo: 1,0 mm). Observou-se elevado percentual de valores acima do percentil 75 em relação ao referencial populacional (16 [76,2%]), sem diferença estatisticamente significante entre o gênero feminino e o masculino (11/15 [73,3%] vs. 5/6 [83,3%]; p=0.550). A comparação entre os ATM heterozigotos e os controles, estratificados por gênero, mostrou que, nos ATM heterozigotos, as mulheres tinham maiores concentrações de HDL-c em comparação aos homens, e valores mais elevados de PCR-us em relação às mulheres controle. Nos ATM heterozigotos, estratificando segundo gênero, a correlação entre HDL-c e PCR-us foi inversamente proporcional e mais forte entre as mulheres, com tendência à significância estatística. Conclusão: Os ATM heterozigotos não diferiram dos controles em relação aos biomarcadores estudados relacionados ao RC. Entretanto, a maioria deles apresentou aumento na espessura do CMIC, preditor independente de morte, risco para infarto do miocárdio e AVC, quando comparado ao referencial para a mesma faixa etária. Esse achado sugere RC nos ATM heterozigotos e aponta para a necessidade de monitoramento da espessura do CMIC e de orientações nutricionais.

Ischemic Stroke in a Patient with Heterozygote Fabry's Disease

It is uncommon for Fabry's disease (FD) patient to present with an isolated ischemic stroke without other typical symptoms or signs of FD. A 48-year-old woman presented with recurrent limb weakness and her brain magnetic resonance imaging revealed multiple ischemic brain lesions. Ten years ago, the patient had been diagnosed with heterozygote FD by the genetic test, but she had not shown any typical symptoms or sign of FD so far. Isolated organ involvement could occur in heterozygote FD.

Assessment of left ventricular function in HeFH patients with myocardial layer-specific analysis based on two-dimensional echocardiography / 中国医学影像技术

Objective To explore the value of layer-specific strain in assessment of left ventricular function in patients with heterozygous familial hypercholesterolemia (HeFH) with normal left ventricular ejection fraction (LVEF).Methods Thirty-four patients with diagnosed HeFH and underwent transthoracic echocardiography were included as HeFH group,while 29 healthy volunteers were taken as control group.EchoPAC software was used to obtain endocardial longitudinal strain (LSendo),myocardial longitudinal strain (LSmyo) and epicardial longitudinal strain (LSepi) of the epicardial,and then statistical analysis was performed.Results LSendo and LSmyo in HeFH group were significantly lower than those in control group (P＜0.001).LSendo and LSmyo were negatively correlated with total cholesterol and low density lipoprotein cholesterol (all P＜0.05).Conclusion Layer-specific strain of left ventricular is of great value in assessing early myocardial damage in patients with HeFH.

A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene / 中华眼底病杂志

Objective To observe the clinical manifestation and gene mutation of a pedigree with Sorsby fundus dystrophy (SFD).Methods Ten members in 3 generations of a pedigree with SFD were included in this study.Four patients were observed in the pedigree,including 2 females and 2 males.All 10 members underwent comprehensive ophthalmic examinations,including best-corrected visual acuity,intraocular pressure,slit-lamp biomicroscopy,indirect ophthalmoscopy,fundus color photography and spectral domain optical coherence tomography.Genomic DNA was extracted from peripheral venous blood which was collected from all the members.Relevant exons of ocular diseases were detected by the next generation sequencing method from the proband.The other members underwent Sanger verification.Results Among the four patients,fading eyesight was appeared at their 44,46,47 and 40 year-old respectively.The two male patients had bilateral morbidity,and the two female patients had monocular symptoms.DNA sequencing results showed that the proband,other 3 patients and 2 members from the Ⅲ generation had heterozygous mutation of TIMP3 gene in exon 5.The amino acid encoded by TIMP3 gene No.204 codon changed from serine to cysteine (TIMP3:NM_000362:Exon5:c.A610T/p.S204C).Coclusions The invasion time of all the patients in this pedigree is after their 40 year-old.Heterozygous mutation at c.610A＞T (p.S204C) in TIMP3 gene is the causative gene of SFD in this pedigree.

Pathogenic gene screening and phenotypic analysis of six albinism families / 中华眼底病杂志

Objective To analyze the pathogenic gene types and phenotypic characteristics of 6 albinism families.Methods A retrospective series of case studies.Six probands of albinism and 20 family members were recruited for this study,5 probands with clinical manifestations of oculocutaneous albinism (OCA) and 1 proband of ocular albinism (OA).Genomic DNA was extracted from peripheral venous blood which was collected from 6 probands and 20 family members.Genetic variations were screened by whole-exome sequencing or Sanger sequencing and then analyzed the relationship between genotypes and phenotypes.Results Genetic sequencing identified 6 potential pathogenic variants in 4 probands,including 2 compound heterozygous mutations in the 2 genes [TYR (c.1037-7T＞A,c.925_c.926insC),OCA2 (c.2359G＞A,c.587T＞C)] associated with OCA1 and OCA2,and 2 hemizygous mutations in the GPR143[GPR143 (c.11C ＞ G),GPR 143 (c.333 G ＞ A)] as sociated with OA 1,respectively.In which,5 were novel mutations and confirmed by Sanger sequencing.One case was accorded with OCA in clinical phenotype,but genetic diagnosis was OA1,the others were agreement between clinical diagnosis and genetic diagnosis.Conclusion There are 4 families with mutations in 6 families,representative of 3 type of albinism (OCA1,OCA2,OA1).

Clinical and genetic analysis of 4 child patients with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD) identified by neonatal screening / 临床检验杂志

Objective To analyze 4 child patients with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD) identified by neonatal screening and confirmed by urine gas chromatography-mass spectrometry (GC/MS) and genetic analysis.Methods Newborns whose C4DC + CSOH concentration was above 0.6 μmol/L in newborn screening were recalled for rescreening,and the CADC + C5OH concentrations in their mothers were detected.The child patients suspected with MCCD were further confirmed by urine GC/MS and genetic analysis.Results Three child patients were definitely diagnosed as MCCD by genetic analysis,including 1 MCCD,1 maternal MCCD and 1 paternal MCCD.The other 1 child patient suspected with MCCD had only one allele in MCCC1.Conclusion The mother and father of newborns with elevated C4DC + C5OH identified in neonatal screening should routinely perform MS / MS testing.When only one pathogenic locus is found in the suspected MCCD child patients by genetic analysis,they should be followed up regularly.

Azathioprine-induced myelosuppression in a pemphigus patient with a heterozygous mutation in the NUDT15 gene / 中华皮肤科杂志

A 49-year-old male patient presented with repeated oral erosions for 1 year,as well as cutaneous erythema and blisters for 1 month.According to histopathological examination and detection of specific antibodies of pemphigus,the patient was diagnosed with pemphigus vulgaris.After the treatment with oral prednisone and azathioprine for 1 month,the white blood cell count and segmented neutrophilic granulocyte count both decreased.After withdrawal of azathioprine,the patient was subcutaneously injected with 150 μg recombinant human granulocyte colony-stimulating factor for 1 session.Then,the white blood cell count became normal.Genotyping test revealed that the patient carried a heterozygous mutation in the NUDT15 gene (JZ274),and was homozygous for wild-type TPMT*2,TPMT*3C and ITPA genes.The patient was diagnosed with azathioprine-induced myelosuppression.

Analysis of G6PD Screening Results in Different Group of the Southeast Dongguan / 现代检验医学杂志

Objective To study different groups of deficiency rate of glucose-6-phosphate dehydrogenase (G6PD)and enzyme activity assay in the detection rate of female heterozygote in the Southeast Dongguan.Methods From January 2007 to April 2013,of 39 475 cases of test results were collected in Tangxia Hospital of Dongguan city,the gene frequency and the detec-tion rate of female heterozygote could be calculated through genetic equilibrium law in different group.Results The male de-ficiency rates of G6PD in different group were Adult group(A)5.03%,Neonatal Group(B)5.10% and Total group(C) 5.06%,respectively,and there were no significant difference between each groups (χ2 =0.0404,P =0.980).The detection rate of female heterozygote of A,B and C in each groups were 27.13%,14.49% and 23.87%,respectively,and the differ-ence were statistically significant between different groups (χ2 =32.26,P =0.000).Conclusion Prevalence of G6PD defi-ciency in this area was 5.06% and there were differences between the deficiency rate of G6PD in different populations.The enzyme activity assay in female heterozygote detection rate is not satisfactory,especially in group B,which is conducive to ge-netic counseling,prenatal diagnosis and birth defects,such as providing more comprehensive information.

Breeding and genotype identification of NLRP3 gene knock-out mice / 第二军医大学学报

Objective: To breed and identify NLRP3 gene knock-out mice. Methods: The NLRP3 gene knock-out heterozygote mice were bred alone and copulated. The offsprings were to have three genotypes: wild genotype, heterozygote genotype and homozygote genotype. Genomic DNA was obtained from each pups and were subjected to PCR and T7 endonuclease 1 to identify the genotype. The homozygote mice were mated with the opposite sex heterozygote mice to obtain more homozygote pups. Results: Breeding and reproducing were both successful, and we obtained heterozygote genotype and homozygote genotype mice with NLRP3 gene knock-out. Conclusion: Correct methods of breeding, reproducing and identifying can effectively obtain NLRP3 gene knock-out mice from heterozygote mice.

Short tandem repeat analysis for diagnosing complete hydatidiform mole and coexisting fetus: a casereport and literature review / 中华围产医学杂志

Objective To investigate the parental origin for a rare case of complete hydatidiform mole and coexisting fetus and to discuss its diagnosis and differential diagnosis.Methods Tissues from the fetus,mole and placenta were collected and pathology analysis and chromosome analysis were done.The DNA from the fetus,mole and parents' peripheral blood leukocytes was amplified with five short tandem repeat (STR) markers (D4S2460,D18S488,D21S2039,DXS1205 and DYS219) at the same time to confirm the parental source of the hydatidiform.Results (1) Casereport:A 27-year-old woman,gravida 1,para 0,was found high risk for neural tube defects at 20 weeks of gestation.At 24+5 weeks of gestation,ultrasound examination demonstrated a normal fetus,a normal placenta and a huge mass with a multicystic appearance attached to the placenta with an obvious demarcation.The fetus died at 26 weeks of gestation.Serum human chorionic gonadotropin-β(β -hCG) level decreased obviously during the first two weeks after artificial induction,but elevated at the third week,and β-hCG titers fell to normal after 2 courses of chemotherapy.Fetus autopsy showed no structure abnormality.Histopathologic examination of the hydatidiform showed swelling of chorionic villi with hyperplasia of the trophoblast and formation of central cisterns suggesting of a twin pregnancy consisting of a complete hydatidiform mole and coexisting fetus.(2) Genetic analysis:The karyotype analysis of the normal placental villi was 46,XY; the cell cultures of fetal cartilage tissue and hydatidiform were failed.STR analysis showed that the fetus was diploid from biparental source;the mole was androgenetic source.And the mole had locus both from Y and X chromosome of the father,so it was heterozygous.It was suggested that this case was derived from one single oocyte fertilized with three spermatozoas.Conclusions STR analysis could be used to confirm the diagnosis of complete hydatidiform mole and coexisting fetus and to find the pathogenetic rnechanism.

Compound heterozygous mutations of a family with inherited hypofibrinogenemia / 中华检验医学杂志

Objective To analyze the phenotype and genotype of a Chinese family with inherited hypofibrinogenemia,and to investigate its molecular mechanism.Methods Peripheral blood was collected from seven people of this family and then plasma was separated.Activated partial thromboplastin time ( APTT),prothrombin time ( PT),thrombin time ( TT),reptilase time ( RT),the activities of antithrombin( AT∶ A ),protein C ( PC ∶ A ) and protein S ( PS ∶ A ) were tested.The activity and antigen of plasma fibrinogen were analyzed by Clauss method and immunoturbidimetry method,respectively.The fibrinogen peptide chain of the proband was semiquantitatively assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE).Thrombin generation test was performed by calibrated automated thromhogram.The dynamic process of blood coagulation was evaluated by the thrombelastography (TEG).Genomic DNA was extracted from the peripheral blood.The sequences of all the exons and exon-intron boundaries of the three fibrinogen genes FGA,FGB and FGG were amplified by polymerase chain reaction ( PCR ) and analyzed by direct sequen(c)ing.Results The activity and the antigen levels of the proband' s plasma fibrinogen were reduced to 0.48 g/L and 0.68 g/L,respectively.TT prolonged to 29.2 s and RT prolonged to 75.8 s.The assays of SDS-PAGE showed no abnormal molecular weight of fibrinogen.Peak height of thrombin generation was reduced to 249.93 nmol/L and endogenous thrombin potential was reduced to 1007.0 nmol · L-1 · min.Hypocoagulability state of the whole blood was found by TEG test.The coagulation index was - 8.6.The proband was diagnosed as inherited hypofibrinogenemia by phenotype analysis.Two mutations (Gln143Pro and g.4642delC) were found in the proband's fibrinogen Aa-chain gene,Gln143Pro came from her mother and g.4642delC came form her father.Conclusion Compound Heterozygous Mutations (Gln143Pro and g.4642delC ) of fibrinogen Aa-chain causes the proband congenital hypofibrinogenemia.

Benign Recurrent Intrahepatic Cholestasis with a Single Heterozygote Mutation in the ATP8B1 Gene / 대한소아소화기영양학회지

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive inherited disorder characterized by multiple recurrent episodes of severe cholestatic jaundice without obstruction of extrahepatic bile duct. We present the case of a 7-year-old boy with BRIC confirmed by mutation analysis in the ATP8B1 gene and typical clinical manifestation. Despite inheritance of BRIC, we detected a mutation on only one allele. To our knowledge, this is the first report of BRIC with a confirmed single heterozygote novel mutation in the ATP8B1 gene in Korea.

Lipodistrofia parcial familiar do tipo Dunnigan: atenção ao diagnóstico precoce / Dunnigan-type familial partial lipodystrophy: attention to precocious diagnosis

A lipodistrofia parcial familiar tipo Dunnigan é uma doença autossômica dominante rara. Em sua forma clássica, é resultante de uma mutação missense heterozigótica no gene LMNA, que codifica a proteína nuclear denominada lâmina tipo A/C. Caracteriza-se pelo desaparecimento progressivo do tecido adiposo subcutâneo nos membros, região glútea, abdome e tronco, que se inicia na puberdade, acompanhado de acúmulo de gordura em outras áreas, como a face, queixo, grandes lábios e região intra-abdominal, conferindo o aspecto de hipertrofia muscular e simulando o fenótipo de síndrome de Cushing. Mulheres afetadas são particularmente predispostas à resistência à insulina e suas complicações, incluindo sinais da síndrome dos ovários policísticos. Com o objetivo de alertar para o diagnóstico precoce, que possibilita a adoção de medidas que minimizam os graves distúrbios metabólicos vinculados à desordem, relatamos o caso de uma paciente em que a investigação foi realizada somente ao final da quinta década de vida. A aparente hipertrofia muscular e o acentuado depósito de gordura nos grandes lábios possibilitam aos médicos ginecologistas a suspeita diagnóstica.

Dunnigan-type familial partial lipodystrophy (FPLD) is an autosomal dominant disease that results from heterozygous missense mutations in LMNA, the gene that encodes nuclear lamin A/C. FPLD is characterized by a progressive disappearance of subcutaneous adipose tissue in the limbs, gluteal region, abdomen and trunk, beginning at the time of or after puberty, and excessive amount of fat in the face, chin, labia majora, and intra-abdominal region, leading to a Cushingoid appearance and increased muscularity phenotype. Affected women are particularly predisposed to insulin resistance and its complications, including features of polycystic ovary syndrome. To emphasize the importance of an early FPLD diagnosis, which is necessary to prevent serious metabolic disturbances, we report a woman diagnosed at about 50 years of age. Increased muscularity and significant labia majora fat deposit made the diagnosis possible by gynecologists.

Analysis of compound heterozygous mutation of low-density lipoprotein receptor gene in two patients with familial hypercholesterolemia / 中华检验医学杂志

Objective To determine LDLR gene mutation in 2 clinically diagnosed FH patients from Hubei province and provide basis for gene diagnosis of FH.Methods Clinical data of 2 FH patients and their parents were collected.The promoter region and exon 1 to exon 18 region of LDLR gene were amplified through PCR and the amplified products were analyzed by forward and reverse DNA sequencing.The mutations were identified after comparison with LDLR gene sequence in GenBank.The pathogenic gene mutations were confirmed according to both genotype and phenotype of FH probands.Results The levels of plasma TC of two probands were 12.79 and 11.98 mmol/L.respectively.No gene mutations were detected in region 3 500 to 3 531 of ApoB100. The mutations of LDLR gene were compound heterozygous mutations. The novel mutation 665G > T detected in the exon 4 of No. 1 proband's LDLR gene was heterozygous missense mutation. The novel mutation 1 358 +32C > T was detected in the exon 9 of No. 1 proband's LDLR gene.The mutations 665G > T ( paternal origin) and 1 358 + 32C > T ( maternal origin) were inherited from the parents. A novel mutation 1 257 C > A was detected in the exon 9 of No. 2 proband's LDLR gene, resulting the presence of a premature termination codon, which was different from 1 257 C > G reported in Belgium.Another heterozygous missense mutation 1 879 G > A was detected in exon 13. They were derived from paternal origin and maternal origin, respectively. Conclusions There are three novel gene mutations:665G >T, 1 358 +32C > T, 1 257C > A found in two probands with compound heterozygous mutations in LDLR respectively. They maybe play a potential role in FH pathogensis.

Analysis of TGFBI gene mutation in a Chinese family with Avellino corneal dystrophies / 中华实验眼科杂志

Background Researches demonstrated that corneal dystrophy is associated with the mutation of transforming growth factor beta induced gene(TGFBI)located at chromosome 5q31 domine.Recent study showed that the gene mutation location is in R124H of TGFBI gene. Objective This study was to identify the mutation characteristics of TGFBI gene in a Chinese family with Avellino corneal dystrophy. Methods This Chinese family with Avellino corneal dystrophy were determined and surveyed in Peking University Third Hospital.Periphery blood from 8 patients with Avellino corneal dystrophy and 2 unaffected subjects were collected from a Chinese family with corneal dystrophy for the extraction of DNA.Exons 4,11,12 of the TGFBI gene were amplified by polymerase chain reaction(PCR),and the amplified products were sequenced directly and compared the gene sequence with that of TGFBI in GenBank.Written informed consent was obtained from each Subject prior to any medieal process. Results This family included 27 members of consecutive 4 generation.The hereditary pattern W88 in accordance with the autosomal dominant inheritance.Directly sequencing of 8 affected members revealed a G tO A transition at codon 124 (CGC to CAC),producing R124H mutation of TGFBI gene.Two synonymous single nucleotide polymorphism(SNP)of TGFBI gene occurred in the family.including a C to T transition at eodon 472(CTC to CTT)in 8 members,and a T to C transition at codon 540(TTT>TTC)in 9 members,which wag unrelated with disease. Conclusion R124H mutation of the TGFBI gene is found in this Chinese family with Avellino corneal dystrophy.

Identification of Compound Heterozygous Mutation in a Korean Patient with Alpha 1-antitrypsin Deficiency / 대한진단검사의학회지

Alpha 1-antitrypsin (AAT) deficiency is a genetic disorder that primarily affects the lungs and liver. While AAT deficiency is one of the most common genetic disorders in the Caucasian population, it is extremely rare in Asians. Here, we report the case of a 36-year-old Korean woman with AAT deficiency who visited the emergency department of our hospital for the treatment of progressive dyspnea that had begun 10 years ago. She had never smoked. Chest computed tomography revealed panlobular emphysema in both lungs, which suggested AAT deficiency. The serum AAT level was 33 mg/dL (reference interval: 90-200 mg/dL). Four exons of the SERPINA1 gene, which is responsible for AAT deficiency, and their flanking regions were analyzed by PCR-direct sequencing. The patient was found to have 1 missense mutation (c.230C>T, p.Ser77Phe; Siiyama) and 1 frameshift mutation (c.1158dupC, p.Glu387ArgfsX14; QOclayton). This is the first Korean case of AAT deficiency confirmed by genetic analysis and the second case of a compound heterozygote of Siiyama and QOclayton, the first case of which was reported from Japan.