scholarly journals Prediction of recessive inheritance for missense variants in human disease

2021 ◽  
Author(s):  
Ben O. Petrazzini ◽  
Daniel J. Balick ◽  
Iain S. Forrest ◽  
Judy Cho ◽  
Ghislain Rocheleau ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Operating Characteristic ◽  
Autosomal Dominant ◽  
Autosomal Recessive Disease ◽  
External Validation ◽  
Discrimination Performance ◽  
Information Need ◽  
Missense Variants ◽  
Validation Set ◽  
Mode Of Inheritance

The prediction of pathogenic human missense variants has improved in recent years, but a more granular level of variant characterization is required. Further axes of information need to be incorporated in order to advance the genotype-to-phenotype map. Recent efforts have developed mode of inheritance prediction tools; however, these lack robust validation and their discrimination performance does not support clinical utility, with evidence of them being fundamentally insensitive to recessive acting diseases. Here, we present MOI-Pred, a three-way variant-level mode of inheritance prediction tool aimed at recessive identification for missense variants. MOI-Pred shows strong ability to discriminate missense variants causing autosomal recessive disease (area under the receiver operating characteristic (AUROC)=0.99 and sensitivity=0.85) in an external validation set. Additionally, we introduce an electronic health record (EHR)-based validation approach using real-world clinical data and show that our recessive predictions are enriched for recessive associations with human diseases, demonstrating utility of our method. Mode of inheritance predictions; pathogenic for autosomal recessive (AR) disease, pathogenic for autosomal dominant (AD) disease, or benign, for all possible missense variants in the human genome are available at https://github.com/rondolab/MOI-Pred/.

Pyloroduodenal Atresia (Diaphragm Type): An Autosomal Recessive Disease

PEDIATRICS ◽  
1978 ◽  
Vol 62 (3) ◽  
pp. 419-421
Author(s):  
Henry C. Mishalany ◽  
Ziad H. Idriss ◽  
Vazken M. Der Kaloustian
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Single Individual ◽  
Autosomal Recessive Mode ◽  
Genetic Etiology ◽  
New Evidence ◽  
Mode Of Inheritance

In 1970,1 1971,2 and 19743 we described two families, each with two siblings who had atresia of the first portion of the duodenum. The four patients were first cousins to each other. We suggested a genetic etiology with an autosomal recessive mode of inheritance, which has been accepted.4 The source of the proposed gene for both families was traced to a single individual. Recently, a third family, linked to the previous two with strong consanguineous ties, had a pair of twins affected with the same anomaly. The purpose of this article is to bring the weight of new evidence afforded by this third family to further substantiate the genetic etiology of this condition.

THE ICHTHYOSIFORM DERMATOSES

PEDIATRICS ◽  
1968 ◽  
Vol 42 (6) ◽  
pp. 990-1004
Author(s):  
Nancy B. Esterly
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Clinical Investigation ◽  
Correct Diagnosis ◽  
Associated Anomalies ◽  
Dominant Trait ◽  
Autosomal Dominant Trait ◽  
Clinical Variants ◽  
Congenital Ichthyosiform Erythroderma ◽  
Mode Of Inheritance

The Term ichthyosis describes a group of heritable disorders which are characterized by cutaneous scaling. The visible scale differentiates these disorders from xeroderma in which the skin is dry but does not visibly desquamate. Many classifications of the ichthyoses have been proposed, but most are descriptive and contribute little to an understanding of etiology and pathogenesis. Often clinical variants or patients with minor associated anomalies have been categorized separately on an empirical basis and, in some cases, several names have been used for one entity to indicate severity of involvement. The most useful classification appears to be that of Wells and Kerr,1 who segregated the various types by their pattern of inheritance and retained the nomenclature in common usage. Differences in clinical features and histologic patterns also correlate with these genetically distinguishable types. Thus, with careful attention to the distribution and type of scale, family history, and skin histology, the physician will be able to classify patients in a meaningful way. Such an approach is helpful for several reasons. The prognosis, troublesome features, and degree of handicapping differ for the various ichthyoses. Sensible genetic counseling, an important part of the management of such patients, is possible only with the correct diagnosis. Moreover, clinical investigation of affected individuals will be further confused unless the entity under study is well defined. The need for an understanding of the physiologic and biochemical defects of ichthvotic skin is underscored by the limitations of currently available therapy. The four major types of ichthyosis include: (1) ichthyosis vulgaris, transmitted as an autosomal dominant trait; (2) sexlinked ichthyosis, transmitted as an Xlinked trait; (3) bullous congenital ichthyosiform erythroderma (CIE), inherited as an autosomal dominant trait; and (4) nonbulbus congenital ichthyosiform erythroderma, autosomal recessive mode of inheritance (Table I).

scholarly journals Split-hand/split-foot malformation (SHFM)

2014 ◽  
Vol 6 (1) ◽  
pp. 122-123
Author(s):  
Monojit Mondal ◽  
Kriti Sundar Rana ◽  
Nayan Banerji ◽  
Sayan Bose ◽  
Tanmoy Biswas ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Mode ◽  
Medical Sciences ◽  
Limb Malformation ◽  
Median Cleft ◽  
Congenital Limb ◽  
Mode Of Inheritance

 Split-hand/split-foot malformation (SHFM), also known as ectrodactyly or lobster claw hand is a congenital limb malformation, characterized by a deep median cleft of the hand and/or foot due to the absence of the central rays of the autopod. It may occur singly or in association with syndromes, former being mostly autosomal dominant but autosomal recessive variety is rare. We are reporting a case of ectrodactyly with autosomal recessive mode of inheritance DOI: http://dx.doi.org/10.3126/ajms.v6i1.10018   Asian Journal of Medical Sciences Vol.6(1) 2015 122-123  

scholarly journals Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns

2015 ◽  
Author(s):  
Tychele Turner ◽  
Christopher Douville ◽  
Dewey Kim ◽  
Peter D Stenson ◽  
David N Cooper ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Distribution Patterns ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Disease Etiology ◽  
Missense Variants ◽  
Significant Difference

The role of rare missense variants in disease causation remains difficult to interpret. We explore whether the clustering pattern of rare missense variants (MAF<0.01) in a protein is associated with mode of inheritance. Mutations in genes associated with autosomal dominant (AD) conditions are known to result in either loss or gain of function, whereas mutations in genes associated with autosomal recessive (AR) conditions invariably result in loss of function. Loss- of-function mutations tend to be distributed uniformly along protein sequence, while gain-of- function mutations tend to localize to key regions. It has not previously been ascertained whether these patterns hold in general for rare missense mutations. We consider the extent to which rare missense variants are located within annotated protein domains and whether they form clusters, using a new unbiased method called CLUstering by Mutation Position (CLUMP). These approaches quantified a significant difference in clustering between AD and AR diseases. Proteins linked to AD diseases exhibited more clustering of rare missense mutations than those linked to AR diseases (Wilcoxon P=5.7x10-4, permutation P=8.4x10-4). Rare missense mutation in proteins linked to either AD or AR diseases were more clustered than controls (1000G) (Wilcoxon P=2.8x10-15 for AD and P=4.5x10-4 for AR, permutation P=3.1x10-12 for AD and P=0.03 for AR). Differences in clustering patterns persisted even after removal of the most prominent genes. Testing for such non-random patterns may reveal novel aspects of disease etiology in large sample studies.

scholarly journals Congenital true leukonychia totalis

2020 ◽  
Vol 6 (3) ◽  
pp. 436
Author(s):  
B. M. Vyshak ◽  
Snehal B. Lunge
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Systemic Disease ◽  
Dominant Mode ◽  
Hodgkin's Lymphoma ◽  
Systemic Diseases ◽  
Leopard Syndrome ◽  
Epiphyseal Dysplasia ◽  
Hereditary Condition ◽  
Mode Of Inheritance

<p>Congenital true leukonychia totalis is very rare hereditary condition characterized by milky white discoloration of all nails. It has mainly autosomal dominant mode of inheritance and autosomal recessive in few cases. It may be inherited or associated with systemic disease or idiopathic. It has been linked to the mutations in PLCD1 gene on chromosome 3p21.3-p22. Leukonychia totalis is associated with multiple systemic diseases such as congenital hyperparathyroidism, Hodgkin's lymphoma, Leopard syndrome, Epiphyseal dysplasia syndrome, Bart Pumphrey syndrome etc. we report a case of sporadic congenital leukonychia totalis in a 24 years female without any systemic abnormalities.</p>

Mode of inheritance of syndactyly in selected human families in Bahawalnagar, Pakistan

2021 ◽  
Vol 7 (2) ◽  
pp. 97-104
Keyword(s):  
Live Birth ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Family Members ◽  
Sample Population ◽  
Type I ◽  
Mode Of Inheritance ◽  
Autosomal Recessive Pattern

Syndactyly is joining or merging of web in feet and hands digits. It is inherited by autosomal dominant, autosomal recessive, x-linked, and y-linked manner. Its prevalence is around 1 in 2000 live birth. Non-syndromic syndactyly is classified into nine types. In this study, we find out prevalence, percentage, types, and mode of inheritance of syndactyly in families of district Bahawalnagar. The survey was carried out in hospitals, schools, and villages of district Bahawalnagar to find out the patients with congenital syndactyly. Three families with cousin marriages were selected for pedigrees. These families had 2:1 of foot and hand syndactyly. The percentage of complete and incomplete syndactyly was recorded 50% in all families. The mode of inheritance was autosomal dominant and autosomal recessive pattern because of two types of syndactyly type I (SD1) and syndactyly type I-c. In families Bwn1, Bwn2, and Bwn3 the percentage of family members associated with syndactyly was 16%, 9.7%, and 6.89% respectively. It was further noted that all male members of all families were affected with syndactyly. This study finds out the type I (SD1) and type I-c syndactyly in the studied sample population.

scholarly journals Clinical experience of observation and tactics of management of a patient with ectodermal angydrotic dysplasia

2021 ◽  
Vol 24 (2) ◽  
pp. 179-186
Author(s):  
Elena Y. Startseva ◽  
Olga V. Bobrova ◽  
Olga I. Letyaeva ◽  
Oleg R. Ziganshin ◽  
Ksenia K. Zakomoldina
Keyword(s):  
Nervous System ◽  
Autosomal Recessive ◽  
Clinical Observation ◽  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Ectodermal Dysplasias ◽  
Wide Range ◽  
Epidermal Growth ◽  
Mode Of Inheritance ◽  
Autosomal Recessive Manner

The concept of ectodermal dysplasias covers a group of rare hereditary developmental anomalies that have a variety of phenotypic variants, but are characterized by common signs of underdevelopment or abnormal formation of organs and tissues derived from the ectodermal layer (skin and its derivatives - nails, hair, teeth, nervous system and sensory organs) ... Approximately 25% of ectodermal dysplasias known to date are inherited in an autosomal dominant or autosomal recessive manner; in other cases, the mode of inheritance is unclear. The syndrome is characterized by a wide range of clinical manifestations and may include additional symptoms of damage to other ectodermal, mesodermal, and endodermal structures. Ectodermal anomalies are a manifestation of disturbances in spatial-temporal coordination during the development of the epidermis. They involve genes such as EGF (epidermal growth factor), ED1 (ectodisplasin), EDAR (anhydrotic receptor ectodysplasin 1) and others that regulate the activity of genes involved in epidermal morphogenesis by activating or suppressing transcription factors (in particular, pb3; Koster). So far, only about 20% of genes have been identified that are responsible for about 200 ectodermal dysplasias of various symptoms and severity. This article describes the clinical observation of a patient with a rare disease - ectodermal anhydrotic dysplasia. The literature data on the clinical features of the course of this dermatosis, as well as the features of the course in this patient are presented.

Familial vocal fold paralysis

2002 ◽  
Vol 116 (12) ◽  
pp. 1047-1049 ◽  
Author(s):  
S. Ali Raza ◽  
S. Mahendran ◽  
Nazneen Rahman ◽  
R. G. Williams
Keyword(s):  
Vocal Fold ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Karyotype Analysis ◽  
Rare Condition ◽  
Vocal Fold Paralysis ◽  
Autosomal Recessive Mode ◽  
Review Of The Literature ◽  
Familial Clustering ◽  
Mode Of Inheritance

Familial clustering of congenital bilateral abductor vocal fold paralysis has been reported very rarely. So far, only a handful of cases have been reported, mostly with the autosomal dominant of X-linked recessive mode of inheritance. We describe the cases of a brother and sister, who presented with neonatal stridor due to bilateral abductor vocal fold paralysis. First-degree parental consanguinity suggests an autosomal recessive mode of inheritance. Karyotype analysis revealed a paracentric balanced inversion of chromosome 13 in both cases, that was also present in the unaffected mother. An updated review of the literature on this interesting but rare condition is also presented.

Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented?

2001 ◽  
Vol 21 (5) ◽  
pp. 430-440 ◽  
Author(s):  
Ira D. Davis ◽  
Katherine MacRae Dell ◽  
William E. Sweeney ◽  
Ellis D. Avner
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Polycystic Kidney

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

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