Case Report: Amyloidosis Cutis Dyschromica: Dermoscopy and Reflectance Confocal Microscopy and Gene Mutation Analysis of a Chinese Pedigree

Background: Amyloidosis cutis dyschromica (ACD) is a rare type of primary localized cutaneous amyloidosis. Non-invasive techniques can provide important clues for early diagnosis.Objectives: To highlight the characteristic imaging changes of ACD under dermoscopy and reflectance confocal microscopy (RCM), investigate gene mutations in a Chinese Han pedigree of ACD, and analyze the genotype–phenotype correlation.Methods: Dermoscopy and RCM examinations were completed together for the pedigree, and the imaging characteristics were described. The diagnosis of ACD was confirmed by pathological examination. Sequencing was performed followed by bioinformatics and genotype–phenotype correlation. ACD-related articles published on PubMed between January 1970 and March 2021 were reviewed and summarized.Results: In ACD, dermoscopy showed patchy white hypopigmentation and brownish spots, stripes, or hyperpigmented blotches and patches. RCM showed a highly refractive substance with clumpy, dotted, and linear structures inside the papillary dermis. Sequencing identified glycoprotein non-metastatic melanoma protein B (GPNMB) missense mutations [c.393T>G (p.Y131X; NM_001005340.2)] and a frameshift deletion mutation [c.719_720delTG (p.V240fs; NM_001005340.2)]. The ANNOtate VARiation (ANNOVAR) software predicted that c.393T>G is a pathogenic mutation. The literature review found 14 mutations, namely, 5 (35.7%) frameshift mutations, 4 (28.6%) non-sense mutations, 4 (28.6%) missense mutations, and 1 (7.1%) splice site mutation. Blisters and epidermolysis were observed in several cases, but there was no significant association between clinical manifestations and mutations in ACD.Conclusions: This study was the first to combine dermoscopy and RCM to describe ACD. Two GPNMB gene mutations were reported in a Chinese ACD pedigree. The genotype–phenotype correlation was analyzed for the first time; however, there was no significant correlation.

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Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

BMC Medical Genomics ◽

10.1186/s12920-021-00944-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xi Luo ◽

Xiang-mei Zhang ◽

Liu-song Wu ◽

Jindong Chen ◽

Yan Chen

Keyword(s):

Genetic Counseling ◽

Peripheral Blood ◽

Clinical Phenotype ◽

Globin Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

Guizhou Province ◽

Globin Genes ◽

Phenotype Correlation ◽

Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

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A bioinformatics framework for genotype–phenotype correlation in humans with Marfan syndrome caused by FBN1 gene mutations

Journal of Biomedical Informatics ◽

10.1016/j.jbi.2005.06.001 ◽

2006 ◽

Vol 39 (2) ◽

pp. 171-183 ◽

Cited By ~ 8

Author(s):

Christian Baumgartner ◽

Gábor Mátyás ◽

Beat Steinmann ◽

Martin Eberle ◽

Jörg I. Stein ◽

...

Keyword(s):

Marfan Syndrome ◽

Gene Mutations ◽

Phenotype Correlation ◽

Fbn1 Gene ◽

Genotype Phenotype Correlation

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Genotype–phenotype correlation of PAX6 gene mutations in aniridia

Human Genome Variation ◽

10.1038/hgv.2015.52 ◽

2016 ◽

Vol 3 (1) ◽

Cited By ~ 25

Author(s):

Tadashi Yokoi ◽

Sachiko Nishina ◽

Maki Fukami ◽

Tsutomu Ogata ◽

Katsuhiro Hosono ◽

...

Keyword(s):

Gene Mutations ◽

Pax6 Gene ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation

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Genotype Phenotype Correlation in Thalassemia Syndromes and Their Correlation with Xmn-1 Polymorphism.

Blood ◽

10.1182/blood.v106.11.3845.3845 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3845-3845

Author(s):

Anupam Sachdeva ◽

Aditya Raina ◽

Varinder Kumar Khanna ◽

Subhash Chander Arya ◽

Satya Prakash Yadav ◽

...

Keyword(s):

Blood Group ◽

Genetic Diseases ◽

Clinical Manifestations ◽

Age At Diagnosis ◽

Beta Thalassemia ◽

Clinical Parameters ◽

Phenotype Correlation ◽

Inherited Disorders ◽

Genotype Phenotype Correlation ◽

High Degree

Abstract Among the inherited disorders of blood, thalassemia constitutes a major bulk of genetic diseases in India. It causes a high degree of morbidity. In a study conducted in India it has been estimated that there is a frequency of 1:2700 at the time of birth. Thus on an average 9000 new thalassemics are born every year in India.. The present study has been aimed at investigating the clinical and hematological spectrum in the above syndrome. It also assessed the prevalence of Xmn -1 polymorphism its relationship with various mutations and its role in modifying the clinical manifestations. The study was conducted on fifty patients representing 49 families and consisting of 33 males and 17 females who were homozygous for beta thalassemia and ranged in age from 3 months to 32 years. The patients were screened for common Indian mutations and their Xmn polymorphism status and this was correlated with their clinical parameters. Apositive correlation in presence of Xmn-1 polymorphism and IVS1-1 mutation was noted. There was also a correlation between age at diagnosis and also the age at first transfusion. There was a correlation between Xmn polymorphism and IVS1-1 mutation. This was found most commonly in the Punjabi Khatri community. None of the patients with blood group O had positivity of Xmn polymorphism. There was no correlation between Xmn and hemoglobin at diagnosis, HbF at diagnosis, MCV at diagnosis, amount of blood in mL/Kg/year and sex and religion.

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Frequency of three common card15/Nod 2 gene mutations and genotype/ phenotype correlation in a single center german IBD cohort

Gastroenterology ◽

10.1016/s0016-5085(03)81905-4 ◽

2003 ◽

Vol 124 (4) ◽

pp. A376

Author(s):

Fabian Schnitzler ◽

Peter Lohse ◽

Michael Sackmann ◽

Burkhard Goeke ◽

Thomas Ochsenkuhn

Keyword(s):

Gene Mutations ◽

Single Center ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation

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Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease

10.21203/rs.3.rs-135373/v1 ◽

2021 ◽

Author(s):

Mingming Li ◽

Jing Ma ◽

Wenlong Wang ◽

Xu Yang ◽

Kaizhong Luo

Keyword(s):

Wilson Disease ◽

Large Scale ◽

Allelic Frequency ◽

Chinese Patients ◽

Missense Mutations ◽

Onset Age ◽

Phenotype Correlation ◽

Novel Mutations ◽

Nonsense Mutations ◽

Genotype Phenotype Correlation

Abstract AIM To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype-phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 7 mutations had not been previously reported: 1510_1511insA, 2075T>C (Leu692Pro), 2233C>A (Leu745Met), 3209C>G (Pro1070Arg),3677C>T (Thr1226Ile), 3793G>T (Val1265Leu) and 3824T>C (Leu1275Ser). The 2333G>T (Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by 2975C>T (Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The 2333G>T (Arg778 Leu) and 2975C>T (Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hot spot exons. Phenotype-genotype correlation analysis suggested that 2333G>T (Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P=0.034). 2975C>T (Pro992Leu) was correlated with earlier age of disease onset (P=0.002). Additionally, we found that the 3809A>G (Asn1270Ser) mutation significantly indicated younger onset age (P=0.012), and the 3884C>T (Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P=0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P=0.039, P=0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified seven novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

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A Novel Missense Variant of HOXD13 Caused Atypical Synpolydactyly by Impairing the Downstream Gene Expression and Literature Review for Genotype–Phenotype Correlations

Frontiers in Genetics ◽

10.3389/fgene.2021.731278 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ruiji Guo ◽

Xia Fang ◽

Hailei Mao ◽

Bin Sun ◽

Jiateng Zhou ◽

...

Keyword(s):

Limb Development ◽

Missense Variant ◽

Missense Mutations ◽

Loss Of Function ◽

Phenotype Correlation ◽

Mutation Site ◽

Genotype Phenotype Correlation ◽

Α Helix ◽

Severe Degree ◽

Hands And Feet

Synpolydactyly (SPD) is a hereditary congenital limb malformation with distinct syndactyly designated as SPD1, SPD2, and SPD3. SPD1 is caused by mutations of HOXD13, which is a homeobox transcription factor crucial for limb development. More than 143 SPD patients have been reported to carry HOXD13 mutations, but there is a lack of genotype–phenotype correlation. We report a novel missense mutation of c. 925A > T (p.I309F) in an individual with atypical synpolydactyly inherited from her father with mild clinodactyly and three other different alanine insertion mutations in HOXD13 identified by whole exome sequencing (WES) in 12 Chinese SPD families. Unlike polyalanine extension, which tends to form α-helix and causes protein aggregation in the cytoplasm as shown by molecular simulation and immunofluorescence, the c. 925A > T mutation impairs downstream transcription of EPHA7. We compiled literature findings and analyzed genotype–phenotype features in 173 SPD individuals of 53 families, including 12 newly identified families. Among the HOXD13-related individuals, mutations were distributed in three regions: polyalanine, homeobox, and non-homeobox. Polyalanine extension was the most common variant (45%), followed by missense mutations (32%) mostly in the homeobox compared with the loss-of-function (LOF) variants more likely in non-homeobox. Furthermore, a more severe degree and classic SPD were associated with polyalanine mutations although missense variants were associated with brachydactyly and syndactyly in hands and feet and LOF variants with clinodactyly in hands. Our study broadens the HOXD13 mutation spectrum and reveals the profile of three different variants and their severity of SPD, the genotype–phenotype correlation related to the HOXD13 mutation site provides clinical insight, including for genetic counseling.

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Clinical study on 7 cases of polypoid endometriosis. PEM: a mimic of malignancy, the symptoms of adenomyosis, endometrial polyps and infertility can assist in diagnosis

10.21203/rs.3.rs-461814/v1 ◽

2021 ◽

Author(s):

Xiaohua Zheng ◽

Ying Xu ◽

xianjing chen ◽

Qibing Zheng ◽

Rong Zhao ◽

...

Keyword(s):

Age Of Onset ◽

Malignant Tumors ◽

Clinical Manifestations ◽

Pelvic Mass ◽

Abnormal Uterine Bleeding ◽

Diagnostic Methods ◽

Pathological Examination ◽

Rare Type ◽

Endometrial Polyps ◽

Polypoid Endometriosis

Abstract Objective: polypoid endometriosis (PEM) is a rare type of endometriosis (EMs), which is easy to be misdiagnosed. The purpose of this paper is to investigate the clinical features and diagnostic methods of PEM. Methods:The clinical data of 7 patients with PEM who were treated at Fujian Provincial Maternity and Children’s Hospital in China within July 2017 to December 2020 period were retrospectively analyzed, and their clinical characteristics, diagnosis, treatment and prognosis were summarized. Results: The age of onset was 31-41 (38.00 ± 1.72) years. There were 5 cases with adenomyosis, 4 cases with endometrial polyps and infertility. The clinical manifestations were diverse. Most of them were pelvic mass, compression symptoms and signs, dysmenorrhea and abnormal uterine bleeding, and three of them were similar to malignant tumors. The gross pathological features were cysts, endogenous or exogenous polypoid masses, which were all composed of endometrioid glands and stromal components, but more diverse than ordinary em. All the 7 patients were confirmed by operation and pathology. Conclusion: PEM is often complicated with adenomyosis, endometrial polyps and infertility. Pathological examination is the gold standard for diagnosis. Imaging examination is easy to be misdiagnosed. Abnormal increase of CA125 can assist in diagnosis.

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