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Journal of Genetic Counseling Dec 2022This focused revision builds on the expert opinions from the original publications of 'Recommendations for human standardized pedigree nomenclature' published in 1995... (Review)
Review
Practice resource-focused revision: Standardized pedigree nomenclature update centered on sex and gender inclusivity: A practice resource of the National Society of Genetic Counselors.
This focused revision builds on the expert opinions from the original publications of 'Recommendations for human standardized pedigree nomenclature' published in 1995 and updated in 2008. Our review of medical publications since 2008 did not identify any fundamental systematic alternative pedigree nomenclature. These findings attest to the relevance of most of the nomenclature with the critical exception of the nomenclature used to denote sex assigned at birth and gender. While we are not recommending the creation of any new pedigree symbols, a major focus of this publication is clarification of the use of symbols and language in the description of the distinction between sex and gender, with a view to ensuring safe and inclusive practice for people who are gender-diverse or transgender. In addition, we recommend modifications to the way that carrier status is depicted. Our goal is to respect individual differences and identities while maintaining biologically, clinically, and genetically meaningful information.
Topics: Male; Female; Infant, Newborn; Humans; Counselors; Pedigree; Gender Identity; Transgender Persons; Societies
PubMed: 36106433
DOI: 10.1002/jgc4.1621 -
Human Mutation Dec 2022Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal...
Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.
Topics: Humans; Exome Sequencing; Eye Proteins; East Asian People; Mutation; Pedigree; Cone-Rod Dystrophies; Retinal Diseases; Macular Degeneration; DNA Mutational Analysis
PubMed: 36284460
DOI: 10.1002/humu.24492 -
Science (New York, N.Y.) Oct 2019
Topics: Forensic Genetics; Humans; Law Enforcement; Pedigree; United States
PubMed: 31601745
DOI: 10.1126/science.aaz6578 -
The Journal of Pediatrics Dec 2023
Topics: Humans; Nails, Malformed; Pedigree
PubMed: 37562741
DOI: 10.1016/j.jpeds.2023.113664 -
Taiwanese Journal of Obstetrics &... Mar 2022To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic...
OBJECTIVES
To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees.
MATERIALS AND METHODS
Gene analyses were performed for 244 pedigrees. There are 130 pedigrees, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis.
RESULTS
Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methylmalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without homocysteine. MMACHC, MMUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 fetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants. The follow-up results were consistent with the prenatal diagnosis.
CONCLUSION
The present study indicates genetic heterogeneity in MMA patients. Genetic analysis is a convenient method for prenatal diagnosis that will aid in avoiding the delivery of MMA patients.
Topics: Amino Acid Metabolism, Inborn Errors; China; Female; Genotype; Humans; Nucleocytoplasmic Transport Proteins; Oxidoreductases; Pedigree; Pregnancy; Prenatal Diagnosis
PubMed: 35361390
DOI: 10.1016/j.tjog.2022.02.017 -
JAMA Ophthalmology Dec 2021
Topics: Albinism, Oculocutaneous; Humans; Pedigree
PubMed: 34910112
DOI: 10.1001/jamaophthalmol.2021.4068 -
JAMA Feb 2022
Topics: Cardiomyopathy, Dilated; Humans; Mass Screening; Pedigree
PubMed: 35103786
DOI: 10.1001/jama.2021.23960 -
Bioinformatics (Oxford, England) Jul 2023The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how...
MOTIVATION
The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how genes influence phenotypic variation, fitness adaptation, and population dynamics.
RESULTS
The AGHmatrix software is an R package focused on the construction of pedigree (A matrix) and/or molecular markers (G matrix), with the possibility of building a combined matrix of pedigree corrected by molecular markers (H matrix). Designed to estimate the relationships for any ploidy level, the software also includes auxiliary functions related to filtering molecular markers, and checks pedigree errors in large data sets. After computing the relationship matrices, results from the AGHmatrix can be used in different contexts, including on prediction of (genomic) estimated breeding values and genome-wide association studies.
AVAILABILITY AND IMPLEMENTATION
AGHmatrix v2.1.0 is available under GPL-3 license in CRAN at https://cran.r-project.org/web/packages/AGHmatrix/index.html and also in GitHub at https://github.com/rramadeu/AGHmatrix. It has a comprehensive tutorial, and it follows with real data examples.
Topics: Genome-Wide Association Study; Software; Genomics; Ploidies; Pedigree
PubMed: 37471595
DOI: 10.1093/bioinformatics/btad445 -
Neurological Sciences : Official... Jun 2023Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene.... (Review)
Review
Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene. In this review, we summarize recent developments in the inheritance features, pathogenesis, and histopathologic and radiologic features of NIID that subvert the previous perceptions of NIID. GGC repeat sizes determine the age of onset and clinical phenotypes of NIID patients. Anticipation may be absent in NIID but paternal bias is observed in NIID pedigrees. Eosinophilic intranuclear inclusions in skin tissues once considered pathological hallmarks of NIID can also present in other GGC repeat diseases. Diffusion-weighted imaging (DWI) hyperintensity along the corticomedullary junction once considered the imaging hallmark of NIID can frequently be absent in muscle weakness and parkinsonism phenotype of NIID. Besides, DWI abnormalities can appear years after the onset of predominant symptoms and may even disappear completely with disease progression. Moreover, continuous reports of NOTCH2NLC GGC expansions in patients with other neurodegenerative diseases lead to the proposal of a new concept of NOTCH2NLC-related GGC repeat expansion disorders (NRED). However, by reviewing the previous literature, we point out the limitations of these studies and provide evidence that these patients are actually suffering from neurodegenerative phenotypes of NIID.
Topics: Humans; Intranuclear Inclusion Bodies; Neurodegenerative Diseases; Diffusion Magnetic Resonance Imaging; Pedigree
PubMed: 36795299
DOI: 10.1007/s10072-023-06677-0 -
American Journal of Medical Genetics.... May 2023Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven... (Review)
Review
Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies.
Topics: Pregnancy; Female; Humans; Child; Phenotype; Ciliopathies; Pedigree; Adaptor Proteins, Signal Transducing
PubMed: 36826837
DOI: 10.1002/ajmg.a.63150