Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
1.
Ann Lab Med ; 42(2): 274-277, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635619

RESUMO

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disease caused by abnormal CAG repeat expansion in the ataxin 1 gene (ATXN1). The presence of CAT interruption(s) is important for diagnosing SCA1 in patients with 39-44 repeat alleles, as only uninterrupted alleles are considered abnormal. Determining the CAT interruption status might also be important for patients with >44 repeats, as the length of the longest uninterrupted CAG repeat stretch has been correlated with age at SCA1 onset. We detected CAT interruption(s) in the archived samples of Korean SCA1 patients using a traditional restriction enzyme method and validated the usefulness of a fluorescence-based tethering PCR procedure. Among the 2,312 alleles analyzed from 1,156 patients, we found 17 expanded alleles with ≥39 repeats, 71% of which harbored 39-44 repeats. Restriction enzyme method of six samples (four with 39-44 repeats and two with >44 repeats) revealed that none of the expanded alleles had CAT interruption(s). Tethering PCR showed the characteristic electropherogram pattern expected without CAT interruption(s). Along with the enzyme restriction method, tethering PCR can be applied to determine the number of allele repeats and provide information on CAT interruption(s) in clinical laboratories.


Assuntos
Ataxina-1 , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Alelos , Ataxina-1/genética , Humanos , Reação em Cadeia da Polimerase , República da Coreia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Degenerações Espinocerebelares/genética
2.
Genes (Basel) ; 12(10)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34680973

RESUMO

Stickler syndrome is an inherited connective tissue disorder of collagen. There are relatively few reports of East Asian patients, and no large-scale studies have been conducted in Korean patients yet. In this study, we retrospectively analyzed the genetic characteristics and clinical features of Korean Stickler syndrome patients. Among 37 genetically confirmed Stickler syndrome patients, 21 types of gene variants were identified, of which 12 were novel variants. A total of 30 people had variants in the COL2A1 gene and 7 had variants in the COL11A1 gene. Among the types of pathogenic variants, missense variants were found in 11, nonsense variants in 8, and splice site variants in 7. Splicing variants were frequently associated with retinal detachment (71%) followed by missense variants. This is the first large-scale study of Koreans with Stickler syndrome, which will expand the spectrum of genetic variations of Stickler syndrome.

3.
Mol Genet Genomic Med ; 9(11): e1838, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34655177

RESUMO

BACKGROUND: Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX-like), and ZNF143 (cblX-like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high-risk couples since the disorder can be life-threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing. METHODS: Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus. RESULTS: Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73*)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203*)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth. CONCLUSION: We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family.

4.
Genomics ; 113(6): 4136-4148, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34715294

RESUMO

Hereditary Spastic Paraplegias (HSP) are a group of rare inherited neurological disorders characterized by progressive loss of corticospinal motor-tract function. Numerous patients with HSP remain undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel genetic variations related to HSP is needed. In this study, we identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families. Fifty-six percent were known HSP genes, and 44% were composed of putative candidate HSP genes involved in the HSPome and originally reported neuron-related genes, not previously diagnosed in HSP patients. Their inheritance modes were 39, de novo; 33, autosomal dominant; and 10, autosomal recessive. Notably, ALDH18A1 showed the second highest frequency. Fourteen known HSP genes were firstly reported in Koreans, with some of their variants being predictive of HSP-causing protein malfunction. SPAST and REEP1 mutants with unknown function induced neurite abnormality. Further, 54 HSP-related genes were closely linked to the HSP progression-related network. Additionally, the genetic spectrum and variation of known HSP genes differed across ethnic groups. These results expand the genetic spectrum for HSP and may contribute to the accurate diagnosis and treatment for rare HSP.

6.
Genes (Basel) ; 12(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34573290

RESUMO

Neurofibromatosis type 1, characterized by neurofibromas and café-au-lait macules, is one of the most common genetic disorders caused by pathogenic NF1 variants. Because of the high proportion of splicing mutations in NF1, identifying variants that alter splicing may be an essential issue for laboratories. Here, we investigated the sensitivity and specificity of SpliceAI, a recently introduced in silico splicing prediction algorithm in conjunction with other in silico tools. We evaluated 285 NF1 variants identified from 653 patients. The effect on variants on splicing alteration was confirmed by complementary DNA sequencing followed by genomic DNA sequencing. For in silico prediction of splicing effects, we used SpliceAI, MaxEntScan (MES), and Splice Site Finder-like (SSF). The sensitivity and specificity of SpliceAI were 94.5% and 94.3%, respectively, with a cut-off value of Δ Score > 0.22. The area under the curve of SpliceAI was 0.975 (p < 0.0001). Combined analysis of MES/SSF showed a sensitivity of 83.6% and specificity of 82.5%. The concordance rate between SpliceAI and MES/SSF was 84.2%. SpliceAI showed better performance for the prediction of splicing alteration for NF1 variants compared with MES/SSF. As a convenient web-based tool, SpliceAI may be helpful in clinical laboratories conducting DNA-based NF1 sequencing.

7.
J Virol Methods ; 298: 114304, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34592335

RESUMO

The potential co-circulation of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) could pose an unprecedented challenge to healthcare systems worldwide. Here, we compared the performance of the PowerChek SARS-CoV-2, Influenza A&B, RSV Multiplex Real-time PCR Kit (PowerChek) for simultaneous detection of SARS-CoV-2, influenza A and B, and respiratory syncytial virus with that of BioFire Respiratory Panel 2.1 (RP2.1) using 175 nasopharyngeal swab (NPS) specimens. Positive percent agreement and negative percent agreement of the PowerChek assay compared to RP2.1 were as follows: 100 % (40/40) and 100 % (135/135) for SARS-CoV-2; 100 % (39/39) and 100 % (136/136) for influenza A; 100 % (35/35) and 100 % (140/140) for influenza B; and 93.1 % (27/29) and 100 % (146/146) for RSV, respectively. The limit of detection (LOD) was accessed using RNA standards for each virus, and the LOD values of the PowerChek assay for SARS-CoV-2, influenza A and B, and RSV were 0.36, 1.24, 0.09, and 0.63 copies/µL, respectively. Our results demonstrate that the PowerChek assay is sensitive and accurate for detection of SARS-CoV-2, influenza A and B, and RSV, suggesting that this assay can be a valuable diagnostic tool when SARS-CoV-2, influenza, and RSV are co-circulating.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Nasofaringe , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/genética , SARS-CoV-2 , Sensibilidade e Especificidade
8.
Nutrients ; 13(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34579037

RESUMO

Vitamin A and carotenoids are fat-soluble micronutrients that play important role as powerful antioxidants modulating oxidative stress and cancer development. Breast cancer is the most common malignancy in women. As the risk of breast cancer is dependent on various lifestyle factors such as dietary modifications, there is increasing interest surrounding the anti-cancerous properties of vitamin A and carotenoids. Despite the suggested protective roles of vitamin A and carotenoids in breast cancer development, their clinical application for the prevention and treatment of breast cancer is limited. In this narrative review, we discuss the roles of vitamin A and carotenoids along with the evaluation method of vitamin A status. We also exhibit the association of genetic variations involved in metabolism of vitamin A and carotenoids with cancers and other diseases. We demonstrate the epidemiological evidence for the relationship of vitamin A and carotenoids with breast cancer risk, their effects on cancer mechanism, and the recent updates in clinical practice of vitamin A or carotenoids as a potential therapeutic agent against breast cancer. This review provides insight into the preventive and therapeutic roles of vitamin A and carotenoids in breast cancer development and progression.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Carotenoides/farmacologia , Vitamina A/farmacologia , Carotenoides/administração & dosagem , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Estado Nutricional , Vitamina A/administração & dosagem
9.
BMC Med Genomics ; 14(1): 204, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404412

RESUMO

BACKGROUND: Ataxia-telangiectasia is a rare autosomal recessive, neurodegenerative disorder caused by alterations in the ATM gene. The majority of ATM pathogenic variants are frameshift or nonsense variants which are predicted to truncate the whole ATM protein. Herein, we report on an ataxia telangiectasia child with atypical phenotype who was identified as compound heterozygous for two ATM variants involving a previously described pathogenic single nucleotide variation (SNV) and a novel copy number variation (CNV). CASE PRESENTATION: A 6-year-old boy presented with delayed development and oculomotor apraxia. Brain magnetic resonance imaging showed interval development of mild atrophy in the cerebellum. Serum alpha fetoprotein level was in normal range. Next-generation sequencing and single-nucleotide polymorphism array tests were performed. Next-generation sequencing revealed a heterozygous nonsense pathogenic variant in ATM, c.742C > T (p.Arg248Ter) inherited from the father. Single-nucleotide polymorphism array revealed a compound heterozygous CNV, arr[GRCh37] 11q22.3(10851766-108183226) × 1, 31460 bp (exons 24-40 deletion of ATM) inherited from the mother, which was validated by reverse transcription-polymerase chain reaction analysis (RT-PCR). We demonstrated that this variant (NM_000051.4:c.3403_6006del) generated a product of in-frame deletion of exon 24-40 of ATM (p.Ser1135_Gln2002del). CONCLUSIONS: The compound heterozygosity for ATM variants involving a previously described pathogenic SNV and a novel CNV may be associated with the atypical clinical manifestations. This clinical report extends the genetic and phenotypic spectrum of ATM pathogenic variants in atypical ataxia-telangiectasia, thus making implementation of advanced analysis beyond the routine next-generation sequencing an important consideration in diagnosis and rehabilitation services for children with ataxia-telangiectasia.

10.
J Alzheimers Dis ; 83(3): 1025-1031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366354

RESUMO

Atypical psychological symptoms frequently occur in early-onset Alzheimer's disease (EOAD), which makes it difficult to differentiate it from other psychiatric disorders. We report the case of a 28-year-old woman with EOAD, carrying a presenilin-1 mutation (S170P), who was initially misdiagnosed with schizophrenia because of prominent psychiatric symptoms in the first 1-2 years of the disease. Amyloid-ß positron emission tomography (PET) showed remarkably high tracer uptake in the striatum and thalamus. Tau PET showed widespread cortical uptake and relatively low uptake in the subcortical and medial temporal regions. Our case advocates for considering EOAD diagnosis for young patients with psychiatric and atypical cognitive symptoms.

12.
Antioxidants (Basel) ; 10(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199555

RESUMO

The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5-43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry-based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI (n = 28) and non-VAKI control subjects (n = 69), consisting of the infection subgroup (n = 23), CKD subgroup (n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation.

13.
Diagnostics (Basel) ; 11(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199654

RESUMO

Liquid biopsies have increasingly shown clinical utility. Although next-generation sequencing has been widely used for the detection of somatic mutations from plasma, performance characteristics vary by platform. Therefore, thorough validation is mandatory for clinical use. This study aimed to evaluate the analytical validity of the Oncomine Pan-Cancer Cell-Free Assay. A massively parallel sequencing for the assay was performed using the Ion S5 XL System with Ion 540 kit. The analytical sensitivity and precision were evaluated using pre-characterized reference materials. The specificity was evaluated using plasma from healthy subjects. A comparison with the Cobas EGFR Mutation Test v2 was performed using reference materials and plasma from lung cancer patients. For SNVs and short indels, the analytical sensitivities at variant allele frequencies (VAFs) of 0.1%, 0.5%, and 1% were 50%, 93.4%, and 100% with 20 ng of input, respectively. The overall precision of the true positive variants was 98% at a VAF of 1% with 20 ng input. The assay showed a similar sensitivity to that of the Cobas EGFR Mutation Test v2 at a VAF of 0.5% with 20 ng of input and 100% concordance on clinical samples. The Pan-Cancer Cell-Free Assay can be applied to detect EGFR mutations in advanced lung cancer patients, although follow-up studies will be needed to evaluate the analytical validity for other types of genes and aberrations using clinical samples.

14.
Front Genet ; 12: 670608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122524

RESUMO

Skeletal dysplasia (SD), a heterogeneous disease group with rare incidence and various clinical manifestations, is associated with multiple causative genes. For clinicians, accurate diagnosis of SD is clinically and genetically difficult. The development of next-generation sequencing (NGS) has substantially aided in the genetic diagnosis of SD. In this study, we conducted a targeted NGS of 437 genes - included in the nosology of SD published in 2019 - in 31 patients with a suspected SD. The clinical and genetic diagnoses were confirmed in 16 out of the 31 patients, and the diagnostic yield was 51.9%. In these patients, 18 pathogenic variants were found in 13 genes (COL2A1, MYH3, COMP, MATN3, CTSK, EBP, CLCN7, COL1A2, EXT1, TGFBR1, SMAD3, FIG4, and ARID1B), of which, four were novel variants. The diagnosis rate was very high in patients with a suspected familial SD and with radiological evidence indicating clinical SD (11 out of 15, 73.3%). In patients with skeletal involvement and other clinical manifestations including dysmorphism or multiple congenital anomalies, and various degrees of developmental delay/intellectual disability, the diagnosis rate was low (5 out of 16, 31.2%) but rare syndromic SD could be diagnosed. In conclusion, NGS-based gene panel sequencing can be helpful in diagnosing SD which has clinical and genetic heterogeneity. To increase the diagnostic yield of suspected SD patients, it is important to categorize patients based on the clinical features, family history, and radiographic evidence.

15.
Front Pediatr ; 9: 628190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718301

RESUMO

Herein, we present a rare case of co-occurring Duchenne muscular dystrophy (DMD) and frontometaphyseal dysplasia 1 (FMD1), two different X-linked diseases, in a 7-year-old boy. He presented with proximal muscle weakness and elevated creatine phosphokinase levels. A multiplex ligation-dependent probe amplification study of DMD revealed the de novo duplications of exons 2-37, thereby confirming the diagnosis of DMD. Initial evaluation revealed atypical features, such as facial dysmorphism, multiple joint contractures, and severe scoliosis, at an early age. However, these were overlooked and were assumed to be atypical manifestations of DMD. Then, the patient's maternal cousin was diagnosed with FMD1 with pathogenic missense variant in FLNA (NM_001110556.2: c.3557C>T/p.Ser1186Leu). A family genetic test revealed that the patient and his mother had the same pathogenic variant in FLNA. The patient's atypical manifestations were considered symptoms of FMD1. Therefore, if one disease does not fully explain the patient's clinical features, an expanded genetic study is needed to detect coincidental disease.

16.
Neuro Endocrinol Lett ; 41(6): 285-289, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33714239

RESUMO

Coffin-Siris syndrome (OMIM #135900) is an autosomal dominant inherited disorder, characterized by dysmorphic features, congenital anomalies, and developmental delay. We report the clinical and molecular findings in a patient with Coffin-Siris syndrome. A 3-year-and-6-month-old boy presented with developmental delay, distinctive facial features, hypertrichosis, partial agenesis of the corpus callosum, fifth digit nail hypoplasia, congenital anomalies, and growth retardation. Targeted gene panel sequencing identified a novel heterozygous frameshift mutation c.2147_2148insAC in ARID1B which was predicted as a premature stop codon p. (Gln717Argfs*29). This is the second report of Coffin-Siris syndrome in Korea. Targeted gene panel sequencing can be used as an effective tool for the diagnosis of rare complex syndromes such as Coffin-Siris syndrome.

17.
Clin Nephrol ; 95(4): 215-220, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33560222

RESUMO

Common side effects of mycophenolate mofetil (MMF) are diarrhea, leukopenia, and infectious complication. The polymorphisms of enzymes affecting MMF clearance could be related to MMF toxicity, and in vitro study revealed that high MMF levels might cause endothelial dysfunction. A 7-year-old Korean male with end-stage renal disease on peritoneal dialysis due to mesangial proliferative glomerulonephritis received a kidney transplantation (KT) from a deceased donor, and immunosuppressive medications including MMF, tacrolimus, and methylprednisolone were started after KT. The patient developed oliguria immediately after surgery, and therapeutic plasmapheresis was initiated with continuous renal replacement therapy for the possibility of graft dysfunction and nephrotic syndrome relapse. Renal function recovered 4 days later, but the patient developed ascites. Diagnostic paracentesis revealed findings that were interpreted as uncomplicated ascites in cirrhosis, not of renal origin. Abdominal ultrasonography showed increased parenchymal echogenicity without cirrhotic change in the liver. Based on a case report and differential diagnosis, we replaced MMF with azathioprine, and 4 weeks later a sudden increment in urine output was detected. Eleven months after KT, the patient is free from ascites. The UGT2B7 802 polymorphism was tested, and wild-type UGT2B7 802 was detected, which is related to low MMF clearance. The low clearance of MMF by UGT2B7 802 wild-type polymorphism might have led to MMF toxicity affecting endothelial dysfunction. This case suggests that refractory ascites could be induced by MMF, and endothelial damage is a possible mechanism.


Assuntos
Ascite/induzido quimicamente , Imunossupressores/efeitos adversos , Transplante de Rim , Ácido Micofenólico/efeitos adversos , Azatioprina/uso terapêutico , Criança , Humanos , Imunossupressores/uso terapêutico , Rim/fisiopatologia , Masculino , Ácido Micofenólico/uso terapêutico
18.
Ann Clin Lab Sci ; 50(6): 818-824, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33334799

RESUMO

Baraitser-Winter Cerebro-fronto-facial syndrome (BWCFF, OMIM #243310, #614583) is caused by a heterozygous gain-of-function mutation of ACTB and ACTG1 that encodes actin. The syndrome is characterized by striking facial features, structural brain abnormalities, ocular coloboma, hearing loss, cardiac defects, intellectual disabilities, short stature, and developmental delay. We report a two-year-old girl who had distinctive facial features, including hypertelorism, arched eyebrows, bilateral ptosis, short broad nose with a flat nasal tip, long philtrum, retrognathia, low-set ears, and a thin upper lip. In addition, she also exhibited short stature, pectus excavatum, developmental delay, brain malformation, and hearing loss. Targeted gene panel sequencing identified a de novo heterozygous missense variant c.826G>A (p.Glu276Lys) in ACTB This is the first Korean case of BWCFF with a novel mutation in ACTB.


Assuntos
Actinas/genética , Transtornos do Crescimento/genética , Hidrocefalia/genética , Retardo Mental Ligado ao Cromossomo X/genética , Obesidade/genética , Anormalidades Múltiplas/genética , Actinas/metabolismo , Pré-Escolar , Coloboma/genética , Deficiências do Desenvolvimento/genética , Face , Facies , Feminino , Transtornos do Crescimento/fisiopatologia , Heterozigoto , Humanos , Hidrocefalia/fisiopatologia , Deficiência Intelectual/genética , Retardo Mental Ligado ao Cromossomo X/fisiopatologia , Obesidade/fisiopatologia , República da Coreia , Síndrome
20.
Ann Clin Lab Sci ; 50(5): 691-698, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33067218

RESUMO

Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia (FGD, OMIM # 305400), is an X-linked recessive inheritance, characterized by short stature, facial dysmorphism, and skeletal abnormalities. We report the clinical and molecular analysis of a family with ASS. A 31-month-old boy and his cousin were initially mistaken for having Noonan syndrome owing to short stature and facial dysmorphism. Considering the family history, we suspected the possibility of an X-linked genetic disease and performed targeted gene panel sequencing; a novel hemizygous variant c.1192-1 G>A in FGD1 was identified in both the proband and his cousin. This is the first report of ASS in Korea. Targeted gene panel sequencing can be an effective tool for diagnosing rare complex syndromes, including ASS.


Assuntos
Nanismo/diagnóstico , Nanismo/genética , Face/anormalidades , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Genitália Masculina/anormalidades , Fatores de Troca do Nucleotídeo Guanina/genética , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Anormalidades Múltiplas/genética , Pré-Escolar , Família , Feminino , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Masculino , Mutação/genética , Linhagem , República da Coreia/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...