An isolated hypogonadotropic hypogonadism male with a novel de novo FGFR1 mutation fathered a normal son evidenced by prenatal genetic diagnosis

Andrologia ◽  
2020 ◽  
Vol 52 (11) ◽  
Author(s):  
Hao Xu ◽  
Zongzhe Li ◽  
Taotao Sun ◽  
Yingwei Chen ◽  
Daoqi Wang ◽  
...  
Keyword(s):  
De Novo ◽  
Hypogonadotropic Hypogonadism ◽  
Genetic Diagnosis ◽  
Prenatal Genetic Diagnosis ◽  
Fgfr1 Mutation

scholarly journals Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project

2020 ◽  
Vol 28 (12) ◽  
pp. 1763-1768
Author(s):  
Thomas Bourinaris ◽  
◽  
Damian Smedley ◽  
Valentina Cipriani ◽  
Isabella Sheikh ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
De Novo ◽  
Age At Onset ◽  
Genetic Diagnosis ◽  
Spastic Paraplegia ◽  
Sequencing Data ◽  
Juvenile Form ◽  
Pathogenic Variants ◽  
Degenerative Disorders ◽  
Significant Gene

AbstractHereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions. Over 400 HSP families were recruited to the 100KGP. In order to obtain genetic diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic variants using candidate variants from the Exomiser analysis of the genome sequencing data. A significant gene-disease association was identified for UBAP1 and HSP. Three protein truncating variants were identified in 13 patients from 7 families. All patients presented with juvenile form of pure HSP, with median age at onset 10 years, showing autosomal dominant inheritance or de novo occurrence. Additional clinical features included parkinsonism and learning difficulties, but their association with UBAP1 needs to be established.

scholarly journals Karyomapping allows preimplantation genetic diagnosis of a de-novo deletion undetectable using conventional PGD technology

2015 ◽  
Vol 31 (6) ◽  
pp. 770-775 ◽  
Author(s):  
Carles Giménez ◽  
Jonás Sarasa ◽  
César Arjona ◽  
Ester Vilamajó ◽  
Olga Martínez-Pasarell ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
De Novo ◽  
Genetic Diagnosis

scholarly journals Prenatal Genetic Diagnosis of Severe Perinatal (Lethal) Hypophosphatasia

2007 ◽  
Vol 74 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Atsushi Watanabe ◽  
Seiichi Yamamasu ◽  
Toshiya Shinagawa ◽  
Yumi Suzuki ◽  
Hidehiko Miyake ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Prenatal Genetic Diagnosis

scholarly journals Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders

2018 ◽  
Author(s):  
Lucilla Pizzo ◽  
Matthew Jensen ◽  
Andrew Polyak ◽  
Jill A. Rosenfeld ◽  
Katrin Mannik ◽  
...  
Keyword(s):  
Family History ◽  
Genetic Background ◽  
Rare Variants ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Clinical Information ◽  
Disease Genes ◽  
Complete Evaluation ◽  
Rare Cnvs ◽  
Complex Disorders

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of second-hits compared to those with mild/no family history (p=0.001). The number of secondary variants also correlated with the severity of cognitive impairment in probands carrying pathogenic rare CNVs (n=53) or de novo mutations in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These second-hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for genes affecting cellular and developmental processes.ConclusionAccurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate gene mutation is identified.

Prenatal Genetic Diagnosis for Pediatricians

PEDIATRICS ◽  
1994 ◽  
Vol 93 (6) ◽  
pp. 1010-1015
Author(s):  
Keyword(s):  
Decision Making ◽  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Diagnostic Tests ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Decision Making Process ◽  
Know How ◽  
Prenatal Genetic Diagnosis ◽  
The Family

Pediatricians may be called upon to counsel a family in which prenatal diagnosis is being considered or in which there is a fetus with a genetic disorder. In some settings, the pediatrician may be the primary resource for counseling the family. More frequently, counseling may already have been provided by a clinical geneticist and/or obstetrician. However, because of a previous relationship with the family, the pediatrician may be called upon to review this information and to assist the family in the decision-making process. The pediatrician should be familiar with the principles of prenatal genetic diagnosis and know how to apply them to specific problems in genetic counseling, diagnosis, and management in clinical practice. At the same time, pediatricians should be familiar with resources available in their region for obtaining information about whether and how a specific disorder can be diagnosed and when and where to refer patients for prenatal genetic diagnosis. The technology of prenatal diagnosis is changing rapidly, and genetic consultants can assist pediatricians in the appropriate utilization and interpretation of the diagnostic tests that are available.

scholarly journals The influence of HIV status on prenatal genetic diagnosis choices

2013 ◽  
Vol 103 (12) ◽  
pp. 1027 ◽  
Author(s):  
Justine S Bee ◽  
Merlyn Glass ◽  
Jennifer G R Kromberg ◽  
Arnold L Christianson
Keyword(s):  
Genetic Diagnosis ◽  
Hiv Status ◽  
Prenatal Genetic Diagnosis

scholarly journals Case Report: A de novo CTNNB1 Nonsense Mutation Associated With Neurodevelopmental Disorder, Retinal Detachment, Polydactyly

2020 ◽  
Vol 8 ◽  
Author(s):  
Zhongling KE ◽  
Yanhui CHEN
Keyword(s):  
Retinal Detachment ◽  
Gene Mutation ◽  
De Novo ◽  
Clinical Phenotype ◽  
Neurodevelopmental Disorder ◽  
Genetic Diagnosis ◽  
Spastic Diplegia ◽  
Rehabilitation Training ◽  
Asian Patients ◽  
Insight Into

CTNNB1 gene mutation was firstly reported related to intellectual disability in 2012, to explore the clinical phenotype and genotype characteristics of CTNNB1 mutation, we collected and analyzed the clinical data of a child with a neurodevelopmental disorder caused by a mutation of CTNNB1. The child had dysmorphic features, microcephaly, hypotonia, polydactyly, retinal detachment, and neurodevelopmental disorder, with a de novo mutation of CTNNB1 c.1603C > T, p.R535X. The patient was diagnosed as Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) and was given rehabilitation training. After 4 months of rehabilitation training, she improved in gross motor function. We found that CTNNB1 mutation can cause neurodevelopmental disorder, which could be accompanied by retinal detachment and polydactyly. The retinal detachment had only been reported in two Asian patients, and we firstly reported the phenotype of polydactyly in the CTNNB1 mutation. This report not only helps to expand the clinical phenotype spectrum of the CTNNB1 gene mutation but also prompts a new insight into genetic diagnosis in patients with a neurodevelopmental disorder, retinal detachment, and polydactyly.

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