Application of Karyomapping for the prenatal diagnosis of five families affected with facioscapulohumerial muscular dystrophy type 1 / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of Karyomapping for the prenatal diagnosis of facioscapulohumerial muscular dystrophy type 1 (FSHD1).@*METHODS@#Peripheral blood and chorionic villi samples were collected from five families affected with FSHD1. Linkage-based diagnosis was carried out by using the Karyomapping method. Diagnosis for two fetal samples was carried out with the next-generation optical mapping system.@*RESULTS@#The results of Karyomapping showed that three fetuses inherited the risky 4q35 region of the proband and two fetuses did not. The fetuses of families 1 and 2 received further diagnosis by the next-generation optical mapping system, and the results were consistent with those of Karyomapping.@*CONCLUSION@#Karyomapping has enabled prenatal diagnosis for the five families affected with FSHD1. The method was faster and simpler compared with conventional strategies, though its feasibility still needs further validation. Since there were no SNP loci designed on the Karyomap chip for the DUX4 gene and its 3' flanking regions, misjudgment due to chromosomal recombination could not be completely eliminated. The accuracy of this method still needs further validation.

Mutational analysis of selected high-grade malignancies in a premenopausal gynecologic cancer population: a potential for targeted therapies?

Background: In 2017, there will be 107,000 cases of gynecologic cancer diagnosed in the US with an overall survival of around 70%-most occurring in post-menopausal individuals. In this study, we have examined a younger (≤ 40 years of age) subpopulation of these women with high grade/ high stage gynecologic malignancies, attempting to identify unique genetic abnormalities or combinations thereof through tissue block specimens. This information was then analyzed in light of known target therapies to see if genetic analysis in this setting would yield significant therapeutic advantage. Methods: We retrospectively evaluated patients with high grade/high stage gynecologic cancers (≤ 40 years of age), examined the presence and status of 400 oncogenes and tumors suppressor genes from Formalin-fixed, Paraffin-embedded (FFPE) tissue and functionally classified mutations by SIFT and Polyphen. Results: Twenty women were identified and stratified into positive and negative outcomes. No demographic, clinicopathologic or treatment factors were significant between these groups. Of the 400 genes evaluated, twelve mutations were significant between the groups, six with targeted therapies. Mutations associated with negative outcomes within histologies/locations were evaluated: ERBB3 in epithelial (ovarian), ALK/GPR124/KMT2D in neuroendocrine (ovarian/endometrial), ROS1/EGFR, ROS1/ERBB3/KMT2D/NIRK1 and GPR124 in sarcoma. All negative outcomes were void of mutations in APC/ABL2. A predictive model for negative outcomes in our cohort was developed from these data: AKAP9-/MBD1-/APC-/ABL2- with a mutation load of > 20.5. Conclusions: Unique multi-gene and mutational outcome correlations were identified in our cohort. Resulting complex mutational profiles in distinctly aggressive gynecologic cancers suggested potential for novel therapeutic treatment. Future larger scale studies will be needed to correlate the genotypic and phenotypic features identified here (AU)

Emerging New Phylogenetic Groups of Rabies Virus in Chinese Ferret Badgers / 生物医学与环境科学（英文）

Chinese ferret badger (FB)-transmitted rabies is a serious threat to public health in southeast China. Although mostly associated with dogs, the rabies virus (RABV) presents genetic diversity and has a significantly wide host range in China. Instead of the dog- and wildlife-associated China II lineage in the past decades, the China I lineage has become the main epidemic group hosted and transmitted by dogs. In this study, four new lineages, including 43 RABVs from FBs, have been classified within the dog-dominated China I lineage since 2014. FB RABVs have been previously categorized in the China II lineage. Moreover, FB-hosted viruses seem to have become the main independent FB-associated clade in the phylogenetic tree. This claim suggests that the increasing genetic diversity of RABVs in FBs is a result of the selective pressure from coexisting dog rabies. FB transmission has become complicated and serious with the coexistence of dog rabies. Therefore, apart from targeting FB rabies, priority should be provided by the appropriate state agencies to perform mass immunization of dog against rabies.

Severe acute alcoholic hepatitis and liver transplant: A never-ending mournful story

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called “6-month rule.” This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.

Brachdactyly instigated as a result of mutation in GDF5 and NOG genes in Pakistani population

Objectives: Brachdactyly a genetic disorder associated with the abnormal development of metacarpals, phalanges or both which results in the shortening of hands and feet. Mutations in the contributing genes has been recognized with the majority of the investigated syndromic form of brachdactyly. The current study was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family

Methods: Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was used for the genomic screening and linkage analysis to observe the mutation in genes. The samples were collected from Luckki Marwat district, KPK, while the research study was conducted in the department of Biochemistry, Quaid-IAzam University, Islamabad, Pakistan

Results: After survey, family was identified with brachdactyly type A2 and investigated a heterozygous arginine to glutamine exchange in the growth demarcation factor 5 in all the victim persons. Different types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel GDF5 genes mutations were reported with distinct limb malformation and sequencing of coding region revealed that the mildly affected individuals were heterozygous while the harshly affected individuals were homozygous

Conclusion: The current study reported the genetic variability and concluded that the Brachdacytyly type A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new subtype of brachydactyly [BDB2] was instigated as a result of novel mutations in NOG. The mutation has been reported for the first time in Pakistani population and especially in Pushtoon ethnic population

Análisis de la causalidad en el estudio genético de los trastornos neuropsiquiátricos: revisión narrativa / Causal analysis in the genetic study of neuropsychiatric disorders: Narrative review / Análise da causalidade no estudo genético dos transtornos neuropsiquiátricos: revisão narrativa

Los trastornos neuropsiquiátricos se caracterizan por formas complejas de transmisión genética. El conocimiento de los aspectos básicos de los diseños metodológicos más usados en la investigación sobre la genética de estos trastornos permite al clínico una búsqueda más eficaz de la literatura disponible, así como una mejor lectura crítica y aplicación práctica de los artículos sobre esta área del conocimiento. Esta revisión tiene como objetivo describir los diseños estadísticos-epidemiológicos más utilizados en este ámbito e ilustrar dicha descripción con algunos ejemplos. En concreto, se revisan aspectos metodológicos generales sobre los estudios de gemelos, los estudios de adopción, análisis de pedigríes, estudios de asociación (casos y controles) y análisis de ligamiento genético.

Neuropsychiatric disorders are characterized by complex forms of genetic transmission. Knowledge of the basic aspects of the most commonly used methodological designs used in research on the genetics of these disorders allows the clinician to perform a more effective search of the literature available as well as a better critical reading and practical application of the articles in this field of knowledge. The objectives of this review are to describe the statistical-epidemiological designs that are most commonly used in this field and to illustrate this description with several examples. Specifically, we review the general methodological aspects of twin studies, adoption studies, pedigree analysis, association studies (case-control), and genetic linkage analysis.

Os transtornos neuropsiquiátricos se caracterizam por formas complexas de transmissão genética. O conhecimento dos aspectos básicos dos desenhos metodológicos mais usados na investigação sobre a genética destes transtornos permite ao clínico uma busca mais eficaz da literatura disponível, assim como uma melhora na leitura crítica e na aplicação prática dos artigos sobre esta área do conhecimento. Esta revisão tem como objetivo descrever os desenhos estatísticos-epidemiológicos mais utilizados neste âmbito e ilustrar dita descrição com alguns exemplos. Em concreto, se revisam aspectos metodológicos gerais sobre os estudos de gêmeos, os estudos de adoção, análise de pedigrees, estudos de associação (casos e controles) e análise de ligamento genético.

Development and Molecular Characterization of Novel Polymorphic Genomic DNA SSR Markers in Lentinula edodes

Sixteen genomic DNA simple sequence repeat (SSR) markers of Lentinula edodes were developed from 205 SSR motifs present in 46.1-Mb long L. edodes genome sequences. The number of alleles ranged from 3–14 and the major allele frequency was distributed from 0.17–0.96. The values of observed and expected heterozygosity ranged from 0.00–0.76 and 0.07–0.90, respectively. The polymorphic information content value ranged from 0.07–0.89. A dendrogram, based on 16 SSR markers clustered by the paired hierarchical clustering' method, showed that 33 shiitake cultivars could be divided into three major groups and successfully identified. These SSR markers will contribute to the efficient breeding of this species by providing diversity in shiitake varieties. Furthermore, the genomic information covered by the markers can provide a valuable resource for genetic linkage map construction, molecular mapping, and marker-assisted selection in the shiitake mushroom.

Genetic and prenatal diagnosis for a haemophilia A family with two novel mutations of F8 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To conduct genetic diagnosis for a family affected with hamophilia A.</p><p><b>METHODS</b>Potential mutations of the F8 gene were analyzed with PCR and Sanger sequencing. Carriers of the mutation were identified through linkage analysis using short tandem repeat (STR) markers. Suspected mutations were verified among 100 healthy controls to rule out genetic polymorphism. Prenatal diagnosis was provided based on the above results.</p><p><b>RESULTS</b>Sequencing analysis has identified two mutations, c.1 A>T and c.4 C>T, which have replaced the start codon (ATG) with leucine (TTG) and glutamine (GAA) with the stop codon (TAA), respectively. The same mutations were not found among the 100 healthy controls. The patient's mother and sister were heterozygous for the same mutations. Upon prenatal diagnosis, the fetus was determined as a male and did not harbor the above mutations. Linkage analysis also confirmed that the fetus has inherited the non-risk X chromosome from his maternal grandfather.</p><p><b>CONCLUSION</b>Detection of pathogenic mutations can enable prenatal diagnosis for the disease.</p>

Application of next generation sequencing technology in Mendelian movement disorders / 中南大学学报(医学版)

Next generation sequencing (NGS) has developed very rapidly in the last decade. Compared with Sanger sequencing, NGS has the advantages of high sensitivity and high throughput. Movement disorders are a common type of neurological disease. Although traditional linkage analysis has become a standard method to identify the pathogenic genes in diseases, it is getting difficult to find new pathogenic genes in rare Mendelian disorders, such as movement disorders, due to a lack of appropriate families with high penetrance or enough affected individuals. Thus, NGS is an ideal approach to identify the causal alleles for inherited disorders. NGS is used to identify genes in several diseases and new mutant sites in Mendelian movement disorders. This article reviewed the recent progress in NGS and the use of NGS in Mendelian movement disorders from genome sequencing and transcriptome sequencing. A perspective on how NGS could be employed in rare Mendelian disorders is also provided.

Molecular characterization of X chromosome fragility in idiopathic mental retardation

Background: Fragile X syndrome [FXS] is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or females. Proper molecular diagnosis is a pre-requisite for providing proper counseling advice

Subjects and methods: Sixty-four males with idiopathic mental retardation, ranging in age from 4.2 to 19 years [10.92+/- 4.00] were clinically pre-selected, based on scoring protocol comprising eight features of the syndrome, before molecular testing. A rapid polymerase chain reactionbased screening was applied for detection of expanded FMR1 alleles. Samples that did not yield the normal band lengths were subjected to a second PCR screen. The secondary screen utilizes a chimeric primer demonstrating the presence or absence of an expanded allele

Results: Amplification of FMRI gene by PCR of tested patients revealed that 8 cases [12.5%] have full mutation and 6 cases [9.4%] have premutation. A wide range of Fra X-scoring ranging from 1 to 7 features was detected in examined cases. Significant clinical features included large prominent ears, hyperextensibility of joints and macroorchidism in post pubertal males

Conclusions: A simplified checklist of fragile X should be used for patients with idiopathic MR and those patients above score 3 should be tested for FXS. The diagnostic assay may be used as a screening method for fragile X syndrome being rapid and cost effective compared to other techniques. In addition, screening of all relatives of proven patients should be performed to detect clinically unidentified cases for provision of proper counseling and optimal management of detected cases

Molecular characterisation of the NSP4 gene of group A human rotavirus G2P[4] strains circulating in São Paulo, Brazil, from 1994 and 2006 to 2010

Group A human rotaviruses (HuRVA) are causative agents of acute gastroenteritis. Six viral structural proteins (VPs) and six nonstructural proteins (NSPs) are produced in RV-infected cells. NSP4 is a diarrhoea-inducing viral enterotoxin and NSP4 gene analysis revealed at least 15 (E1-E15) genotypes. This study analysed the NSP4 genetic diversity of HuRVA G2P[4] strains collected in the state of São Paulo (SP) from 1994 and 2006-2010 using reverse transcription-polymerase chain reaction, sequencing and phylogenetic analysis. Forty (97.6%) G2P[4] strains displayed genotype E2; one strain (2.4%) displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P[4]) and the NSP4 (E2) genotype of HuRVA. NSP4 phylogenetic analysis showed distinct clusters, with grouping of most strains by their genotype and collection year, and most strains from SP were clustered together with strains from other Brazilian states. A deduced amino acid sequence alignment for E2 showed many variations in the C-terminal region, including the VP4-binding domain. Considering the ability of NSP4 to generate host immunity, monitoring NSP4 variations, along with those in the VP4 or VP7 protein, is important for evaluating the circulation and pathogenesis of RV. Finally, the presence of one G2P[4]E1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.

Mutations in a Large Pedigree with Y-STR Genetic Markers / 法医学杂志

OBJECTIVE@#To explore the mutation of Y-STR loci in meiotic allelic transmission in a large pedigree.@*METHODS@#The oral swabs of 163 male individuals were collected from a Lin pedigree. Twenty-two Y-STR genetic markers were typed with AGCU Y24 fluorescent detection kit (AGCU Y24 system), which also contained 16 Y-STR markers included in Yfiler multiple amplification kit (Yfiler system). The genotyping results of Y-STR loci were compared between each two males in the pedigree.@*RESULTS@#There were 20 and 30 kinds of haplotypes obtained with Yfiler and AGCU Y24 systems in 163 male individuals from the Lin pedigree, respectively. The rates referred to haplotype differences (RRHD) of these two typing systems between male pairs were 0.910 5 and 0.922 7, respectively. The average number of marker differences were 6.582 1 and 9.824 8, respectively. The RRHD increased along with the incidents of meiosis.@*CONCLUSION@#Y-STR mutation leads to different Y-STR haplotypes among the male members in a paternal pedigree and the rate of difference increases along with the incidents of meiosis.

Establishment of a 15 loci multiplex amplification system and the genetic poly- morphism in Xinjiang Uygur population / 法医学杂志

OBJECTIVE@#To develop a five fluorescence-labeled multiplex amplification system for 15 loci and study genetic polymorphism in Xinjiang Uygur population.@*METHODS@#The STR loci were screened. The alleles were named according to the number of repeats by sequencing. The sensitivity, species specificity, identity and stability of the five fluorescence-labeled multiplex amplification system for the 15 loci were all tested. Then, the genetic polymorphism was analyzed in Xinjiang Uygur population and compared with other ethnic groups including Xizang Tibetan, Xiuyan Manchu, and Guangzhou Han population.@*RESULTS@#The 15 loci multiplex amplification system was established. The sensitivity was 0.3 ng with good species specificity, identity and stability. The distributions of genotype for 13 STR loci in Uygur population were in accordance with Hardy-Weinberg equilibrium with no genetic linkage between these loci. Most loci showed statistically significant among different populations.@*CONCLUSION@#The established system has application value in forensic evidence. The 13 STR loci in Uygur population have

Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.</p><p><b>METHODS</b>To decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years.</p><p><b>RESULTS</b>We identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient.</p><p><b>CONCLUSIONS</b>We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.</p>

Construction of the first genetic linkage map of Salvia miltiorrhiza Bge. using SSR, SRAP and ISSR markers / 药学学报

The first genetic linkage map of Salvia miltiorrhiza was constructed in 94 F1 individuals from an intraspecific cross by using simple sequence repeat (SSR), sequence-related amplified polymorphism (SRAP) and inter-simple sequence repeat (ISSR) markers. A total of 93 marker loci in the linkage map, consisting of 53 SSR, 38 SRAP and 2 ISSR locus were made up of eight linkage groups, covered a total length of 400.1 cm with an average distance of 4.3 cm per marker. The length of linkage groups varied from 3.3 -132 cm and each of them included 2-23 markers, separately. The result will provide important basis for QTL mapping, map-based cloning and association studies for commercially important traits in S. miltiorrhiza.

Correlation of TLR2 and TLR4 gene polymorphisms with the susceptibility and recurrence of condyloma acuminatum / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the correlation of the gene polymorphisms of Toll-like receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma acuminatum (CA).</p><p><b>METHODS</b>Using Snapshot, we detected the gene polymorphisms of TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and 1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative controls. We made comparisons between the CA patients and controls as well as between the cases of recurrent CA and those of non-recurrence at 6 months after treatment.</p><p><b>RESULTS</b>There were 72, 48, and 20 cases of genotype TT, TC, and CC of TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3 cases in the controls. The gene frequency of mutant C was 31. 43% in the patients, significantly higher than 17.62% in the controls (χ2 = 12.04, P < 0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in the non-recurrent cases (χ2 = 4.16, P < 0.05). There were 74, 49, and 17 cases of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients, as compared with 73, 29, and 3 cases in the controls. The gene frequency of mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the controls (χ2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases, markedly higher than 25. 29% in the non-recurrent cases (χ2 = 4.18, P < 0.05). There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G), respectively, in the CA patients, as compared with 26, 58, and 21 cases in the controls. There was no significant difference in the gene frequencies of mutant G between the two groups (χ2 = 0.33, P > 0.05). No mutant genes of TLR2 2508 (G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2 597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93).</p><p><b>CONCLUSION</b>TLR2 597(T/C) is tightly linked to 1350(T/C), which is correlated with both the susceptibility and the recurrence of condyloma acuminatum.</p>

Recent advances in genetic studies of stuttering

Speech and language are uniquely human-specific traits, which contributed to humans becoming the predominant species on earth. Disruptions in the human speech and language function may result in diverse disorders. These include stuttering, aphasia, articulation disorder, spasmodic dysphonia, verbal dyspraxia, dyslexia and specific language impairment. Among these disorders, stuttering is the most common speech disorder characterized by disruptions in the normal flow of speech. Twin, adoption, and family studies have suggested that genetic factors are involved in susceptibility to stuttering. For several decades, multiple genetic studies including linkage analysis were performed to connect causative gene to stuttering, and several genetic studies have revealed the association of specific gene mutation with stuttering. One notable genetic discovery came from the genetic studies in the consanguineous Pakistani families. These studies suggested that mutations in the lysosomal enzyme-targeting pathway genes (GNPTAB, GNPTG and NAPGA) are associated with non-syndromic persistent stuttering. Although these studies have revealed some clues in understanding the genetic causes of stuttering, only a small fraction of patients are affected by these genes. In this study, we summarize recent advances and future challenges in an effort to understand genetic causes underlying stuttering.

Vitiligo - Part 1

Vitiligo is a chronic stigmatizing disease, already known for millennia, which mainly affects melanocytes from epidermis basal layer, leading to the development of hypochromic and achromic patches. Its estimated prevalence is 0.5% worldwide. The involvement of genetic factors controlling susceptibility to vitiligo has been studied over the last decades, and results of previous studies present vitiligo as a complex, multifactorial and polygenic disease. In this context, a few genes, including DDR1, XBP1 and NLRP1 have been consistently and functionally associated with the disease. Notwithstanding, environmental factors that precipitate or maintain the disease are yet to be described. The pathogenesis of vitiligo has not been totally clarified until now and many theories have been proposed. Of these, the autoimmune hypothesis is now the most cited and studied among experts. Dysfunction in metabolic pathways, which could lead to production of toxic metabolites causing damage to melanocytes, has also been investigated. Melanocytes adhesion deficit in patients with vitiligo is mainly speculated by the appearance of Köebner phenomenon, recently, new genes and proteins involved in this deficit have been found.

Hashimoto's Thyroiditis and Papillary Thyroid Cancer / 대한갑상선학회지

The association of Hashimoto's thyroiditis (HT) with papillary thyroid cancer (PTC) has been still under debate. Some suggest that these two are positively correlated, whereas other studies report no relationship. We performed a systematic literature review of original studies to investigate the correlation between HT and PTC. The existing data provide inconsistent evidence favoring a causal relationship between HT and PTC. The average prevalence rate of PTC in patients with HT was 1.2% in 8 fine needle aspiration (FNA) studies of 18,023 specimens and 27.6% in 8 archival thyroidectomy studies of 9884 specimens. The risk ratio of PTC in HT specimens ranged from 0.39 to 1.00 in the FNA group (average RR 0.69) in contrast to 1.15 to 4.16 from thyroidectomy studies (average RR 1.59). Population-based fine needle aspiration biopsy studies report no relationship, whereas many of the studies using thyroidectomy specimens report a positive relationship, possibly related to selection bias. Several studies identified a few biomolecular markers, including the PI3K/Akt pathway, RET/PTC gene rearrangements, p63 protein, and loss of heterozygosity of hOGG1, that are potentially involved in neoplastic transformation from HT to PTC. So far, no causal genetic linkage has been confirmed. PTC with concurrent HT is associated with female gender, young age, less aggressive disease such as small tumor size, less frequent capsular invasion and nodal metastasis, and better outcome. However, more prospective studies with long term follow-up are needed to further elucidate this relationship and prognosis. Careful observation and follow-up of HT patients is recommended, especially those with nodular variants.

Prenatal genetic diagnosis of oculocutaneous albinism type II through mutation detection combined with SNPs linkage analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA), in both of which only 1 pathogenic allele has been identified.</p><p><b>METHODS</b>To determine the clinical classification of OCA through DNA sequencing for TYR, P, TYRP1 and SLC45A2 genes in combination with phenotype analysis. Prenatal diagnosis was carried out by direct sequencing and intragenic SNPs family-based linkage analysis.</p><p><b>RESULTS</b>In the first family, only 1 heterozygous mutation c.1255C>T was found in the proband, which was inherited from her mother. Together with its clinical phenotype, the proband was suspected to have OCA2 Screening of amniotic fluid, however, has found no mutation. With family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. In the second family, again only one heterozygous mutation c.1920_1949 del30bp and ins AACA was found in the proband, which was inherited from her father. Together with its clinical phenotype, the proband was suspected to have OCA2. Screening of amniotic fluid has revealed a heterozygous mutation c.1920_1949 del30bp and ins AACA. By family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. Both fetuses had a normal phenotype at birth.</p><p><b>CONCLUSION</b>Prenatal genetic diagnosis has been provided for the first time for two families affected with OCA, in which only 1 pathogenic mutant allele was detected. The combined mutation detection and SNPs linkage analysis has turned out to be successful.</p>