scholarly journals Cone Dystrophy in Patient with HomozygousRP1L1Mutation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sachiko Kikuchi ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Said El Shamieh ◽  
Keiichiro Akeo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cone Dystrophy ◽  
Homozygous Mutation ◽  
Full Field ◽  
Clinical Evaluations ◽  
Normal Visual Acuity ◽  
Severe Reduction ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Cone Density

The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygousRP1L1mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygousRP1L1mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of thePCDH15,RPGRIP1, andGPR98genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of theRP1L1homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in theRP1L1gene can cause cone dystrophy.

The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Enise Avci Durmusalioglu ◽  
Esra Isik ◽  
Durdugul Ayyildiz Emecen ◽  
Damla Goksen ◽  
Samim Ozen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Diagnostic Process ◽  
Homozygous Mutation ◽  
Lysinuric Protein Intolerance ◽  
Case Presentation ◽  
Lysinuric Protein ◽  
Next Generation Sequencing Ngs ◽  
Protein Intolerance ◽  
Generation Sequencing

Abstract Objectives Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping. Case presentation A fifteen-year-old-boy with an initial diagnosis of osteogenesis imperfecta, was referred due to a number of atypical findings accompanying to osteoporosis such as splenomegaly and bicytopenia. A NGS panel (TruSight One Sequencing Panel) was performed and a novel homozygous mutation of c.257G>A (p.Gly86Glu) in the SLC7A7 gene (NM_001126106.2), responsible for LPI, was detected. The diagnosis was confirmed via reverse phenotyping. Conclusions Reverse phenotyping using a multigene panel shortens the diagnostic process.

scholarly journals Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) using Next Generation Sequencing (NGS)

2021 ◽  
Author(s):  
Ioannis Papoulidis ◽  
Makarios Eleftheriades ◽  
Emmanouil Manolakos ◽  
Simoni Maria Liapi ◽  
Anastasia Konstantinidou ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Tandem Repeats ◽  
Novel Mutation ◽  
Homozygous Mutation ◽  
Primary Microcephaly ◽  
Strong Connection ◽  
C Terminus ◽  
Next Generation Sequencing Ngs ◽  
Autosomal Recessive Primary Microcephaly ◽  
Generation Sequencing

MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.

scholarly journals A Novel p.G141R Mutation in ILDR1 Leads to Recessive Nonsyndromic Deafness DFNB42 in Two Chinese Han Families

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xueling Wang ◽  
Longhao Wang ◽  
Hu Peng ◽  
Tao Yang ◽  
Hao Wu
Keyword(s):  
Sanger Sequencing ◽  
Pcr Amplification ◽  
Homozygous Mutation ◽  
Frequent Mutation ◽  
Nonsyndromic Deafness ◽  
Chinese Han ◽  
Targeted Next Generation Sequencing ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Genetic hearing impairment is highly heterogeneous. In this study, targeted next-generation sequencing (NGS) in two Chinese Han families identified a novel p.G141R homozygous mutation in ILDR1 as the genetic cause of the deafness. Consistent with the recessive inheritance, cosegregation of the p.G141R variant with the hearing loss was confirmed in members of both families by PCR amplification and Sanger sequencing. SNP genotyping analysis suggested that those two families were not closely related. Our study showed that targeted NGS is an effective tool for diagnosis of genetic deafness and that p.G141R in ILDR1 may be a relatively frequent mutation for DFNB42 in Chinese Hans.

Identification and Clinical Implications of a Novel MYO15A Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing

2019 ◽  
Vol 24 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Narges Zarepour ◽  
Mahbobeh Koohiyan ◽  
Afsaneh Taghipour-Sheshdeh ◽  
Fatemeh Nemati-Zargaran ◽  
Nader Saki ◽  
...  
Keyword(s):  
Pedigree Analysis ◽  
Genetic Linkage Analysis ◽  
Clinical Evaluations ◽  
Sequencing Technologies ◽  
The Family ◽  
New Strategy ◽  
Genetics And Genomics ◽  
Next Generation Sequencing Ngs ◽  
Very High ◽  
Generation Sequencing

Background and Objectives: Hereditary hearing loss (HL) is known by a very high genetic heterogeneity, which makes a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Method: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 3 affected members. After excluding mutations in the GJB2 and 7 other most common autosomal recessive nonsyndromic HL genes via Sanger sequencing and genetic linkage analysis in the family, we applied the Otogenetics deafness NGS panel in the proband of this family. Results: NGS results showed a novel rare variant (c.7720C>T) in the MYO15A gene. This nonsense variant in the exon 40 of the MYO15A gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics guideline. Conclusions: New DNA sequencing technologies could lead to identification of the disease causing variants in highly heterogeneous disorders such as HL.

scholarly journals Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1467
Author(s):  
Gema García-García ◽  
Alba Berzal-Serrano ◽  
Piedad García-Díaz ◽  
Rebeca Villanova-Aparisi ◽  
Sara Juárez-Rodríguez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Targeted Ngs ◽  
Syndromic Hearing Loss ◽  
Genetics And Genomics ◽  
Custom Panel ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.

scholarly journals Ataxia with Oculomotor Apraxia Type 4 with PNKP Common “Portuguese” and Novel Mutations in Two Belarusian Families

2019 ◽  
Vol 08 (02) ◽  
pp. 058-062
Author(s):  
Galina Rudenskaya ◽  
Andrey Marakhonov ◽  
Olga Shchagina ◽  
Ekaterina Lozier ◽  
Elena Dadali ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Developmental Delay ◽  
Autosomal Recessive ◽  
Novel Mutations ◽  
Related Disorder ◽  
Oculomotor Apraxia ◽  
Biallelic Mutations ◽  
Next Generation Sequencing Ngs ◽  
Ataxia With Oculomotor Apraxia ◽  
Generation Sequencing

AbstractAtaxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, PNKP-related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous PNKP mutations was c.1123G>T, common in Portuguese patients; biallelic mutations, c.1270_1283dup14 and c.1029+2T>C, respectively, were novel. These are the first reported AOA4 Slavic cases and the first with a “Portuguese” PNKP mutation outside Portugal. Distinction in two brothers was microcephaly but their disease was not severe in contrast to PNKP-related “microcephaly, seizures, and developmental delay” and reported cases with features of both phenotypes.

scholarly journals Case Report: Identification of a Novel Homozygous Mutation in GPD1 Gene of a Chinese Child With Transient Infantile Hypertriglyceridemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Haihua Lin ◽  
Youhong Fang ◽  
Lin Han ◽  
Jie Chen ◽  
Jingan Lou ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Underlying Mechanism ◽  
Causative Factor ◽  
Homozygous Mutation ◽  
Clinical Presentations ◽  
Chinese Girl ◽  
Gpd1 Gene ◽  
Generation Sequencing

Transient infantile hypertriglyceridemia is a rare autosomal recessive disorder characterized by hypertriglyceridemia, hypohepatia, hepatomegaly, hepatic steatosis and fibrosis in infancy. Mutations in GPD1 gene are considered the causative factor but the underlying mechanism of this disorder is still enigmatic. To date, only 24 different GPD1 mutations have been reported in the literature worldwide with transient infantile hypertriglyceridemia or relevant conditions. Here we report a Chinese girl who developed hepatomegaly hepatic steatosis, elevated transaminase and hypertriglyceridemia from the age of 4 months. A novel homozygous variant c.454C>T (p.Q152*) was found in GPD1 gene by next-generation sequencing. This patient is the 3rd Asian reported with transient infantile hypertriglyceridemia. We summarized the clinical presentations of transient infantile hypertriglyceridemia and also expanded the spectrum of disease-causing mutations in GPD1.

scholarly journals Targeted Next Generation Sequencing Identifies Novel Mutations inRP1as a Relatively Common Cause of Autosomal Recessive Rod-Cone Dystrophy

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Said El Shamieh ◽  
Elise Boulanger-Scemama ◽  
Marie-Elise Lancelot ◽  
Aline Antonio ◽  
Vanessa Démontant ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Autosomal Recessive ◽  
Cone Dystrophy ◽  
Next Generation ◽  
Prevalence Studies ◽  
Targeted Next Generation Sequencing ◽  
Retinal Disorders ◽  
Inherited Retinal Disorders ◽  
Generation Sequencing ◽  
Index Cases

We report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD) andRP1mutations. Detailed ophthalmic examination was performed in 242 sporadic and arRCD subjects. Genomic DNA was investigated using our customized next generation sequencing panel targeting up to 123 genes implicated in inherited retinal disorders. Stringent filtering coupled with Sanger sequencing and followed by cosegregation analysis was performed to confirm biallelism and the implication of the most likely disease causing variants. Sequencing identified 9RP1mutations in 7 index cases. Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes. Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD. Our prevalence studies showed thatRP1mutations account for up to 2.5% of arRCD. These results point out for the necessity of sequencingRP1when genetically investigating sporadic and arRCD. It further highlights the interest of unbiased sequencing technique, which allows investigating the implication of the same gene in different modes of inheritance. Finally, it reports that different regions ofRP1can also lead to arRCD.

scholarly journals NGS Gene Panel Analysis Revealed Novel Mutations in Patients with Rare Congenital Diarrheal Disorders

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 262
Author(s):  
Maria Valeria Esposito ◽  
Marika Comegna ◽  
Gustavo Cernera ◽  
Monica Gelzo ◽  
Lorella Paparo ◽  
...  
Keyword(s):  
Clinical Picture ◽  
Autosomal Recessive ◽  
Disease Gene ◽  
Rapid Diagnosis ◽  
Novel Mutations ◽  
Bioinformatic Tools ◽  
Congenital Chloride Diarrhea ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Microvillous Inclusion Disease

Congenital diarrheal disorders (CDDs) are early-onset enteropathies generally inherited as autosomal recessive traits. Most patients with CDDs require rapid diagnosis as they need immediate and specific therapy to avoid a poor prognosis, but their clinical picture is often overlapping with a myriad of nongenetic diarrheal diseases. We developed a next-generation sequencing (NGS) panel for the analysis of 92 CDD-related genes, by which we analyzed patients suspect for CDD, among which were (i) three patients with sucrose-isomaltase deficiency; (ii) four patients with microvillous inclusion disease; (iii) five patients with congenital tufting enteropathy; (iv) eight patients with glucose-galactose malabsorption; (v) five patients with congenital chloride diarrhea. In all cases, we identified the mutations in the disease-gene, among which were several novel mutations for which we defined pathogenicity using a combination of bioinformatic tools. Although CDDs are rare, all together, they have an incidence of about 1%. Considering that the clinical picture of these disorders is often confusing, a CDD-related multigene NGS panel contributes to unequivocal and rapid diagnosis, which also reduces the need for invasive procedures.

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