Liver transplantation for inherited metabolic liver diseases / 器官移植

Inherited metabolic liver disease (IMLD) is a category of liver metabolic diseases caused by genetic disorders. The pathogenesis of IMLD is complex, which primarily comprises the accumulation of harmful metabolic substrates or products caused by specific enzyme defects and energy defects or abnormal deposition caused by abnormal metabolism of glucose, fat and other substances. In recent years, liver transplantation has played an increasingly critical role in the treatment of IMLD with the development of liver transplantation. At present, IMLD has become the second most important indication after biliary atresia in pediatric liver transplantation. Currently, IMLD patients receiving liver transplantation can be divided into two categories: the first category is IMLD complicated with liver disease; Category 2 patients have a normal liver structure but are deficient in related metabolic enzymes. It can not only replace the liver with abnormal structure and function, but also provide normal enzymes required for patients' metabolism, which may improve their quality of life and even save their lives. In this article, common feasible liver transplantation for IMLD, clinical prognosis and surgical procedures of liver transplantation for IMLD were reviewed, aiming to provide reference for liver transplantation for IMLD.

Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service

Purpose: Hereditary causes are an important etiological category of childhood blindness. This study reports the real?world experience of a developing ocular genetic service. Methods: The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North?West India. Children presenting to the genetic clinic with congenital or late?onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel?based sequencing/chromosomal microarray) was outsourced to third?party laboratories with the cost of the test being borne by the patient. Results: Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Conclusion: Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Estado de vacunación en pacientes con riesgo de enfermedades invasoras por bacterias capsuladas en un hospital pediátrico de Buenos Aires / Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires

Introducción. El Ministerio de Salud contempla vacunas específicas para personas con riesgo elevado de infecciones invasoras por bacterias capsuladas (BC). En la actualidad se desconoce el cumplimiento del programa. El objetivo fue evaluar el estado de vacunación para BC en ≤ 18 años con factores de riesgo. Población y métodos. Estudio observacional, analítico, mediante encuesta a padres de ≤ 18 años con VIH, asplenia y/o déficit de complemento que concurrieron al vacunatorio de un hospital pediátrico de octubre de 2020 a septiembre de 2021. Se recabaron datos sociodemográficos y clínicos. Se evaluó el estado de vacunación para BC: neumococo, meningococo y Haemophilus influenzae b (Hib), calendario regular y antigripal. Se administró la escala de reticencia a la vacunación (ERV): rango 10-50. Se analizó la asociación entre las variables estudiadas y la vacunación para BC mediante regresión logística (OR, IC95%). Se utilizó la base datos REDCap® y STATA vs14®. Resultados. Participaron 104 sujetos, media 9,9 años (DE 4,4). Asplenia: 91,3 %, VIH: 7,6 % y déficit de complemento: 0,9 %. Nivel socioeconómico: pobreza relativa: 38,4 %, seguido por clase media: 37,5 %. Estado de vacunación completa para meningococo: 45 %, neumococo: 42 %, Hib: 97 %. El 77,9 % tenía al día el calendario regular y el 61,5 %, el antigripal. Media ERV: 41,9 (DE 3,2). No se encontraron asociaciones significativas entre las variables y el estado de vacunación para BC. Conclusiones. Un elevado porcentaje no tenía vacunación completa para BC, tampoco el calendario regular y antigripal. La confianza en la vacunación de los cuidadores fue elevada.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10­50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

Therapeutic landscape for inherited ocular diseases: Current and emerging therapies

Inherited ocular diseases comprise a heterogeneous group of rare and complex diseases, including inherited retinal diseases (IRDs) and inherited optic neuropathies. Recent success in adeno-associated virus-based gene therapy, voretigene neparvovec (Luxturna®) for RPE65-related IRDs, has heralded rapid evolution in gene therapy platform technologies and strategies, from gene augmentation to RNA editing, as well as gene agnostic approaches such as optogenetics. This review discusses the fundamentals underlying the mode of inheritance, natural history studies and clinical trial outcomes, as well as current and emerging therapies covering gene therapy strategies, cell-based therapies and bionic vision.

Progress of newborn screening in China / 浙江大学学报·医学版

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.

The progress of the gene editing therapy of inherited retinal diseases based on CRISPR/Cas9 / 中华眼底病杂志

Inherited retinal diseases (IRDs) are the major cause of refractory blinding eye diseases, and gene replacement therapy has already made preliminary progress in the treatment of IRDs. For IRDs that cannot be treated by gene replacement therapy, gene editing provides an alternative therapeutic method. Strategies like disruption of pathogenic variants with or without gene augmentation therapy and precise repair of pathogenic variants can be applied for IRDs with various inheritance patterns and pathogenic variants. In animal models of retinitis pigmentosa, Usher syndrome, Leber congenital amaurosis, cone rod cell dystrophy, and other disorders, CRISPR/Cas9, base editing, and prime editing showed the potential to edit pathogenic variations in vivo, indicating a promising future for gene editing therapy of IRDs.

Reinforce revealing missing heritability in the gene of inherited retinal diseases / 中华眼底病杂志

Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Genetic diagnosis has become one essential method for patients with IRD in their clinical management. So far, about 30% of the patients with IRD cannot get molecular diagnosis (no pathogenic variant detected or only mono-allele variant identified in AR genes) using target or whole exome sequencing. Most missing heritability or variants for these patients were variants located in no-coding regions (deep intron or promoter regions) and structure variants of the known IRD genes. It is more challenge to reveal this kind of missing variants, which need using whole genome sequencing combined with other cellular or molecular assays.

Application of CRISPR/Cas9 genome editing technology in hereditary retinal diseases / 中华实验眼科杂志

Several mutant genes for inherited retinal diseases have been identified, but effective treatments are still lacking.The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system can edit human genomic DNA by nonhomologous end joining or homology-directed repair, offering more possibilities for the treatment of hereditary retinal diseases.CRISPR/Cas9 not only can genetically correct patient-derived induced pluripotent stem cells (iPSCs) to observe their differentiation into retinal cells thereby, thereby exploring the pathogenesis of the disease and implementing cell therapy, but can also be delivered to the body via vectors and directly act on target cells to achieve in vivo gene editing.CRISPR/Cas9 gene editing technology in hereditary retinal diseases has been mainly used in retinitis pigmentosa, hereditary X-linked juvenile retinoschisis, and Leber congenital amaurosis 10, of which the in vitro application of CRISPR/Cas9 for Leber congenital amaurosis 10 has entered the clinical trial stage.In this paper, we reviewed the mechanism and key advances of CRISPR/Cas9 and provided an overview of gene editing in IRDs.

Advances of Dupilumab in Treating Rare Monogenic Inherited Skin Diseases / 罕见病研究

Monogenic inherited skin diseases are a group of clinically rare diseases that include nearly 1000 phenotypically distinct disorders. Through the concerted efforts of researchers in dermatological sciences and related disciplines worldwide, many advances have been made in the etiology and pathogenesis of these diseases in the last 30 years. However, it is important to note that the treatment of the majority of monogenic inherited skin diseases remains a challenge for clinicians. Dupilumab is a fully human monoclonal IgG4 antibody that specifically binds to the α subunit of the IL-4 receptor, thereby inhibiting the IL-4 and IL-13 signaling pathway. It was first approved for the treatment of moderate-to-severe atopic dermatitis (AD) and has been used worldwide. In recent years, the drug has been successfully used to treat some monogenic inherited skin diseases with AD-like clinical manifestations, such as hyper-IgE syndrome and Netherton syndrome, with good efficacy. The drug was later tried for the treatment of other monogenic inherited skin diseases, such as Hailey-Hailey syndrome and epidermolysis bullosa pruriginosa, where it was also proven to be effective. In this paper, we review literature reports related to dupilumab for the treatment of monogenic inherited skin diseases in recent years, focusing on its efficacy, safety and possible therapeutic mechanisms. We aim to provide a possible scientific basis for the future application of this drug in the field of rare monogenic inherited skin diseases.

Quality assessment of screening for neonatal inherited metabolic disease in Chaoyang District from 2012 to 2021 / 预防医学

Objective @#To evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District, Beijing Municipality from 2012 to 2021, so as to provide insights into improvements in the screening quality and efficiency of neonatal inherited metabolic diseases. @*Methods@#Data pertaining to screening of neonatal inherited metabolic disease in Chaoyang District from 2012 to 2021 were captured from Beijing Center for Neonatal Disease Screening. The percentage of screening, eligible rate of blood smears collection, re-examination rate of suspected cases, and definitive diagnosis of congenital hypothyroidism (CH), phenylketonuria (PKU) and congenital adrenal hyperplasia (CAH) were analyzed to evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District.@*Results@#There were 484 002 live neonates in Chaoyang District from 2012 to 2021, and 481 395 neonates were screened for inherited metabolic diseases, with a screening rate of 99.46% and 99.71% eligible rate of blood smears collection. A total of 4 305 suspected positive cases were screened, including 4 148 cases recalled for re-examinations, with a 96.35% re-examination rate of suspected cases, and the re-examination rates of CH, PKU and CAH were 96.37%, 96.79% and 95.65%, respectively. Totally 482 neonates were definitively diagnosed with inherited metabolic diseases, with an overall incidence rate of 1/999, and the incidence rates of CH (307 cases), hyperthyrotropinemia (103 cases), PKU (66 cases) and CAH (6 cases) were 1/1 568, 1/4 674, 1/7 294 and 1/20 233, respectively.@*Conclusions@#The screening rate and re-examination rate of neonatal inherited metabolic diseases was both more than 95% in Chaoyang District from 2012 to 2021. Improving the management of neonatal inherited metabolic diseases screening and the recall of suspected cases is required.

Application of live biotherapeutic products and perspective in the treatment of inherited metabolic disease / 生物工程学报

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.

Automated Classification of Inherited Retinal Diseases in Optical Coherence Tomography Images Using Few-shot Learning / 生物医学与环境科学（英文）

OBJECTIVE@#To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs).@*METHODS@#In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples.@*RESULTS@#The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications.@*CONCLUSION@#This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.

Analysis of personalized precision diagnosis of 156 children with suspected rare inherited metabolic diseases / 中国热带医学

@#Abstract: Objective　To explore the accurate diagnosis of children with suspected rare inherited metabolic diseases, and to compare the application value of mass spectrometry and genetic testing in the diagnosis of rare inherited metabolic diseases (IMD). Methods　The clinical information, mass spectrometry, and genetic results of children with suspected rare inherited metabolic diseases admitted to the Department of Pediatrics, the Affiliated Haikou Hospital of Xiangya Medical College, Central South University from March 2017 to December 2021 were analyzed retrospectively. Results　156 children with suspected rare inherited metabolic diseases were detected by mass spectrometry, 67 cases were positive and 89 cases were negative. Children with positive initial examination were retested, and 19 cases were positive. Among the retest positive cases, 13 cases were given genetic testing, and 9 cases were positive and 4 cases were negative. Among the initial negative cases, 54 children with poor therapeutic effect and high clinical suspicion of inherited metabolic diseases completed genetic testing, 15 cases were positive and 39 cases were negative. The results of the two detection methods were compared, the positive rate of mass spectrometry was 19.4%(13/67), and the positive rate of genetic testing was 35.8%(24/67). The continuity correction of Pearson's chi-square test of continuity correction suggested that the results of genetic testing and mass spectrometry were different, and the difference was statistically significant (P<0.05). Taking genetic testing as the gold standard, the sensitivity and specificity of mass spectrometry detection were 37.5% (95%CI:19.6%-59.2%) and 90.7% (95%CI:76.9%-97.0%), respectively. Among the 24 confirmed cases, 5 cases were diagnosed by gene panel and 19 cases were diagnosed by whole exome sequencing (WES). One case diagnosed by WES had no pathogenic mutation detected by gene panel before diagnosis. The detection of DNM1L gene c.1040C>G and AMN gene c.651+1G>C are novel pathogenic gene variants, which have clinical significance. Conclusions　The ability of mass spectrometry in the diagnosis of inherited metabolic diseases is limited. Genetic testing, especially whole exome sequencing, can be the first choice for individualized diagnosis of suspected rare inherited metabolic diseases. In addition, the new mutation sites found by WES in this study enriched the pathogenic gene mutation spectrum and provided direction for further functional biological experiments.

Duchenne muscular dystrophy: case series of rare inherited muscular disorder

Duchenne muscular dystrophy (DMD) is a rare muscular disordercaused by mutation of gene encoding dystrophin protein which required for maintaining muscle stability during contraction. DMD occurs in 1 in 5000 male live births and characterized by progressive muscular weakness associated with motor development delay, loss of independent ambulation, respiratory failure, and cardiomyopathy. We present a case series of 3 DMD patients who were diagnosed at Prof. dr. I.G.N.G. Ngoerah general hospital,Denpasar over a period of four years (2019-2022). Clinical manifestation of patients includes progressive weakness of lower extremities and difficulty to stand up from sitting position. Physical examination revealed pseudohypertrophy of calf, winged scapula, positive Gower抯 sign, and waddling gait in all three cases. Supporting examination showed an increase of alanine transaminaseand aspartate transaminase5.6 times and 6.1 times the upper limit of normal, respectively. Definitive diagnosis of all patient was made based on immunohistochemistry staining which revealed an absent of dystrophin protein around muscle membrane

Clinical Characteristics of Cardiac Arrhythmias in Pediatric Age Group

Background: The Symptomatic manifestation of pediatric arrhythmias varies according to the age. Patients with disturbances in cardiac rhythm have several complaints, but also could be totally asymptomatic. This study aimed to assess clinical characteristics of Tachy and Brady arrhythmia in neonates, infant, children and adolescents of various age groups. Methods: This cross-sectional study included 253 patients of pediatric age below 18 years old presented with different types of tachyarrhythmia or bradyarrhythmia. All patients were subjected to clinical general examination of patient, vital data collection, local cardiac examination, 12 leads electrocardiography, ambulatory ECG Holter monitoring, exercise ECG stress testing if indicated and transthoracic echocardiography. Results: There was a significant relation between age of presentation of the study patients and classification of arrhythmia (P < 0.001). Palpitations was the most common presentations of arrhythmia in our study patients (32%) followed by dyspnea in 17.8 % of the patients. 20.6 % of the study patients with arrhythmias were asymptomatic. Congenital heart anomalies were in 43 % of the patients. Conclusion: Pediatric arrhythmia can be totally asymptomatic and discovered accidentally. Congenital cardiac anomalies and cardiac arrhythmias are closely correlated. Holter monitoring and exercise ECG testing can help in diagnosing pediatric arrhythmia. Untreated or persistent arrhythmia causes LV myopathy and dilatation. Antiarrhythmic drugs can have their harmful effect on the growing child.

Enfoque práctico en el diagnóstico de los errores congénitos del metabolismo / Practical approach to the diagnosis of inherited metabolic diseases

Resumen Los errores congénitos del metabolismo constituyen un grupo creciente de enfermedades poco frecuentes con habitual impacto neurológico. Heterogéneas en el aspecto clínico y bioquímico, su diagnóstico y terapéutica son dificultosos. Los avances en su conocimiento, en los métodos diagnósticos y en sus tratamientos, ponen de relevancia lo importante de un diagnóstico oportuno, puerta del acceso a la inter vención médica temprana. Es muy relevante la sospecha del neuropediatra ante diferentes situaciones clínicas. El presente artículo pretende ser un aporte práctico para facilitar su reconocimiento.

Abstract Inborn errors of metabolism constitute a growing group of rare diseases with usual neurological impact. Hete-rogeneous in clinical and biochemical aspects, its diagnosis and treatment are difficult. Advances in its knowledge, in diagnostic methods and in its treatments, highlight the importance of a timely diagnosis, the gateway to access to early medical intervention. The neuropediatrician's suspicion in different clini cal situations is very relevant. This article aims to be a practical contribution to facilitate their recognition.

Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases

ABSTRACT Background: Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases. Objectives: The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis. Methods: A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal. Results: Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%). Conclusion: Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield.

Approach to inherited hypertrichosis: A brief review

Hypertrichosis refers to the growth of hair, of an excessive amount and thickness, on any part of the body. It must be distinguished from hirsutism which is characterized by excess growth of hair in androgen-dependent areas on the upper lip, chin, chest, linea alba, thigh and axilla. Hypertrichosis may be localized or generalized, and congenital or acquired. Excess hair growth has a psychological impact on the child as well as the parents due to the cosmetic disfigurement it produces. Current treatment options are limited and not wholly satisfactory. Treatment should be customized according to the area, nature and amount of hair growth, age of the patient and personal preferences. In addition, when hypertrichosis occurs as a component of a syndrome, multidisciplinary management is required to address the associated systemic features. A detailed review of inherited generalized hypertrichosis is presented here with emphasis on clinical clues to identifying complex syndromes with multisystem involvement