Identification of a Novel Homozygous Mutation in BBS10 Gene in an Iranian Family with Bardet-Biedl Syndrome

2021 ◽  
Author(s):  
Mohammad Dehani ◽  
Davood Zare-Abdollahi ◽  
Ata Bushehri ◽  
Azadeh Dehghani ◽  
Jalil Effati ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Risk Estimation ◽  
Retinal Dystrophy ◽  
Homozygous Mutation ◽  
Cousin Marriage ◽  
Exon 2 ◽  
Bardet Biedl Syndrome ◽  
Whole Exome ◽  
Iranian Family ◽  
Phenotype Description

Background: Bardet–Biedl Syndrome (BBS) is a rare pleiotropic autosomal recessive disease related to ciliopathies with approximately 25 causative genes. BBS is a multisystemic disorder with wide spectrum of manifestations including truncal obesity, retinal dystrophy, male hypogenitalism, postaxial polydactyly, learning difficulties, and renal abnormalities. Methods: A consanguineous Iranian family with a 28-year-old daughter affected with BBS, resulting from a first cousin marriage, was examined. After clinical examination, Whole Exome Sequencing (WES) was applied. Following the analysis of exome data, Sanger sequencing was used to confirm as well as to co-segregate the candidate variant with the phenotype. Results: A novel homozygous variant [c. 2035G>A (p.E679K)] in exon 2 of the BBS10 gene was found which was categorized as likely pathogenic based on American College of Medical Genetics and Genomics (ACMG) guidelines and criteria. In this study, the variant was fully co-segregated with the phenotype in the family. Conclusion: Despite overlapping with other ciliopathies in terms of the phenotype, the BBS has high genetic heterogeneity and clinical variability even among affected members of a family. The symptoms observed in patients are largely related to the genes involved and the type of mutations in the BBS. In this study, in addition to phenotype description of the proband harboring a novel disease-causing variant in BBS10 gene, the spectrum of BBS symptoms was expanded. The findings of this study can be useful in genetic counseling, especially for risk estimation and prenatal diagnosis.

scholarly journals Rare homozygous mutation in TUBB8 associated with oocyte maturation defect-2 in a consanguineous mating family

2020 ◽  
Author(s):  
Qiong Xing ◽  
Ruyi Wang ◽  
Beili Chen ◽  
Lin Li ◽  
Hong Pan ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Induction Therapy ◽  
Ovulation Induction ◽  
Healthy Woman ◽  
Homozygous Mutation ◽  
Exon 2 ◽  
Whole Exome ◽  
Clinical Detection ◽  
Maturation Defect ◽  
Online Software

Abstract Purpose: Variations in many genes may lead to the occurrence of oocyte maturation defects. To investigate the genetic basis of oocyte maturation defects, we performed clinical and genetic analysis of a pedigree. Methods: The proband with oocyte maturation defect-2 receiving ovulation induction therapy and her parents were selected for clinical detection, whole exome sequencing and Sanger sequencing. One unrelated healthy woman received ovulation induction therapy as control. Mutations were assessed after frequency screening of public exome databases. Then homozygous variants shared by the proband and her parents were selected. Results: Arrest of oocytes maturation was observed. A new missense mutation in TUBB8 (TUBB8: NM_177987: exon 2: c. C161T: p. A54V) was identified, which was shown to be rare compared with public databases. The variant was highly conserved among primates, and was suggested to be deleterious by online software prediction. Conclusions: The homozygote of this variant (TUBB8: NM_ 177987: exon 2:c.C161T: p.A54V) might affect spindle assembly, cause arrest of oocyte maturation and lead to oocyte maturation defect-2.

scholarly journals A Novel Homozygous Variant in GJA1 Causing a Hallermann-Streiff/Oculodentodigital Dysplasia Overlapping Phenotype: A Clinical Report

2021 ◽  
Vol 2 ◽  
Author(s):  
Alexandra Jimenez-Armijo ◽  
Khadja Oumensour ◽  
Bouchra Bousfiha ◽  
Tristan Rey ◽  
Virginie Laugel-Haushalter ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Sleep Apnea Syndrome ◽  
Radiographic Examination ◽  
Homozygous Mutation ◽  
Clinical Report ◽  
Exon 2 ◽  
Whole Exome ◽  
Obstructive Sleep ◽  
Craniofacial Features ◽  
Oculodentodigital Dysplasia

This paper reports the case of a Moroccan girl with a phenotype within the clinical spectrum of both Hallermann-Streiff (HSS, OMIM 234100) and Oculodentodigital Dysplasia (ODDD, OMIM 164200) syndromes. The patient presented with repeated dental abscesses and severe early childhood caries. She had no learning deficit nor psychomotor regression; however, a language delay was noted. She also presented with obstructive sleep apnea syndrome and specific craniofacial features pathognomonic of HSS. Radiographic examination showed enamel and dentin defects, giving a ghost-like tooth appearance. Several clinical features of ODDD overlap those of HSS and may confuse diagnosis, considering that the inheritance of HSS is not described yet. The diagnostic odyssey of this patient ended with the identification by exome sequencing of a novel homozygous alteration in the GJA1 gene. A missense substitution in exon 2 [Chr6(GRCh37): g.121768554C>G NM_000165.4: c.561C>G p.Cys187Trp] was identified by whole-exome sequencing (WES), suggesting a diagnosis of ODDD. This is the first report of a homozygous mutation affecting the second extracellular loop of the CX43 protein.

scholarly journals Bardet Biedl Syndrome

2014 ◽  
Vol 3 (1) ◽  
pp. 56-59
Author(s):  
Abdul Bari ◽  
Aminul Islam ◽  
Mahmud Javed Hasan ◽  
Shanjida Shamsi ◽  
Sultan Ahmed
Keyword(s):  
Wide Spectrum ◽  
Retinal Dystrophy ◽  
Male Hypogonadism ◽  
Community Based ◽  
College Hospital ◽  
Bardet Biedl Syndrome ◽  
Medical College ◽  
Autosomal Recessive Condition ◽  
Characteristic Features ◽  
Criteria For Diagnosis

Bardet Biedl syndrome is a rare autosomal recessive condition with a wide spectrum of clinical features. The accepted major criteria for diagnosis include obesity, polydactyly, male hypogonadism, mental retardation, retinal dystrophy, adrenal dysfunction. We have presented a 14 year old male patient exhibiting characteristic features of Bardet Biedl syndrome (BBS), admitted into Community Based Medical College Hospital. CBMJ 2014 January: Vol. 03 No. 01 P: 56-59

Novel homozygous mutation in TUBB8 associated with oocyte maturation defect-2 in a consanguineous marriage family

2020 ◽  
Author(s):  
Qiong Xing ◽  
Ruyi Wang ◽  
Beili Chen ◽  
Lin Li ◽  
Hong Pan ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Induction Therapy ◽  
Ovulation Induction ◽  
Homozygous Mutation ◽  
Exon 2 ◽  
Whole Exome ◽  
Clinical Detection ◽  
Maturation Defect ◽  
Functional Mechanisms ◽  
Online Software

Abstract Purpose: To study the genetic basis of oocyte maturation defects, we performed clinical and genetic analysis of a pedigree. Variations in many genes may lead to the occurrence of oocyte maturation defects, but the specific functional mechanisms need to be further studied.Methods: One proband with oocyte maturation defect-2 receiving ovulation induction therapy and her parents were selected for clinical detection, whole exome sequencing and Sanger sequencing. One normal woman received ovulation induction therapy. Mutations were assessed after frequency screening of public exome databases. Then homozygous variants shared by the proband and her parents were selected.Results: Arrest of oocytes maturation was observed. A new missense mutation in TUBB8 (TUBB8: NM_177987: exon 2: c. C161T: p. A54V) was identified, which was shown to be novel compared with public databases. The variant was highly conserved among primates, and was suggested to be deleterious by online software prediction. Conclusions: The homozygote of this variant (TUBB8: NM_ 177987: exon 2:c.C161T: p.A54V) might affect spindle assembly, cause arrest of oocyte maturation and lead to oocyte maturation defect-2.

scholarly journals Bardet Biedl Syndrome- A Case Report

1970 ◽  
Vol 20 (1) ◽  
pp. 56-59
Author(s):  
M Azizul Haque ◽  
LS Sharmin ◽  
Q Tarikul Islam ◽  
ARM Saifuddin Ekram
Keyword(s):  
Mental Retardation ◽  
Case Report ◽  
Autosomal Recessive ◽  
Wide Spectrum ◽  
Retinal Dystrophy ◽  
Male Hypogonadism ◽  
Bardet Biedl Syndrome ◽  
Autosomal Recessive Condition ◽  
Characteristic Features ◽  
Criteria For Diagnosis

Bardet Biedl syndrome is a rare autosomal recessive condition with a wide spectrum of clinical features. The accepted major criteria for diagnosis include retinal dystrophy, obesity, polydactyly, male hypogonadism, mental retardation and renal dysfunction. We have presented a 16 year old male patient exhibiting characteristic features of Bardet Biedl syndrome (BBS) and then the literature is reviewed.   doi: 10.3329/taj.v20i1.3092 TAJ 2007; 20(1):56-59

scholarly journals Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohd Fareed ◽  
Vikas Makkar ◽  
Ravi Angral ◽  
Mohammad Afzal ◽  
Gurdarshan Singh
Keyword(s):  
Nephrotic Syndrome ◽  
Disease Management ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Homozygous Mutation ◽  
Consanguineous Family ◽  
Clinical Prognosis ◽  
Whole Exome ◽  
Recurrent Mutations ◽  
Ckd Stage

AbstractNephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9:g.41209497C > T; NM_024876.4:c.748G > A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions: SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.

scholarly journals Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia

2015 ◽  
Vol 104 (2) ◽  
pp. 286-291 ◽  
Author(s):  
Ranjith Ramasamy ◽  
M. Emre Bakırcıoğlu ◽  
Cenk Cengiz ◽  
Ender Karaca ◽  
Jason Scovell ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Homozygous Mutation ◽  
Nonobstructive Azoospermia ◽  
Whole Exome

scholarly journals A homozygous mutation of GNRHR in a familial case diagnosed with polycystic ovary syndrome

2017 ◽  
Vol 176 (5) ◽  
pp. K9-K14 ◽  
Author(s):  
Sandrine Caburet ◽  
Ronit Beck Fruchter ◽  
Bérangère Legois ◽  
Marc Fellous ◽  
Stavit Shalev ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Polycystic Ovary ◽  
Missense Variant ◽  
Genetic Alterations ◽  
Homozygous Mutation ◽  
Gonadotropin Secretion ◽  
Whole Exome ◽  
A Genome

Context PCOS is a heterogeneous condition characterized by hyperandrogenism and chronic anovulation and affects about 10% of women. Its etiology is poorly known, but a dysregulation of gonadotropin secretion is one of its hallmarks. Objective As the etiology of PCOS is unclear, we have performed a genome-wide analysis of a consanguineous family with three sisters diagnosed with PCOS. Methods Whole-exome sequencing and Sanger sequencing confirmation. Results Whole-exome sequencing allowed the detection of the missense variant rs104893836 located in the first coding exon of the GNRHR gene and leading to the p.Gln106Arg (p.Q106R) substitution. Sanger sequencing of all available individuals of the family confirmed that the variant was homozygous in the three affected sisters and heterozygous in both parents. Conclusions This is the first description of a GNRHR gene mutation in patients diagnosed with PCOS. Although we do not exclude a possible interaction of the identified variant with the genetic background and/or the environment, our result suggests that genetic alterations in the hypothalamo–pituitary axis may play role in the pathogenesis of PCOS.

scholarly journals Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis

2018 ◽  
Author(s):  
Jose Velilla ◽  
Michael Mario Marchetti ◽  
Agnes Toth-Petroczy ◽  
Claire Grosgogeat ◽  
Alexis H Bennett ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
In Silico ◽  
Muscular Atrophy ◽  
Structural Modeling ◽  
Recessive Mutation ◽  
Homozygous Mutation ◽  
Functional Studies ◽  
Whole Exome

AbstractObjectiveThe objective of this study is to identify the genetic cause of disease in a congenital form of congenital spinal muscular atrophy and arthrogryposis (CSMAA).MethodsA 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis and diminished lower limb movement. Whole exome sequencing was performed on the proband and family members. In silico modeling of protein structure and heterologous protein expression and cytotoxicity assays were performed to validate pathogenicity of the identified variant.ResultsWhole exome sequencing revealed a homozygous mutation in the TRPV4 gene (c.281C>T; p.S94L). The identification of a recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated disease. p.S94L and other previously identified TRPV4 variants in different protein domains were compared in structural modeling and functional studies. In silico structural modeling suggests that the p.S94L mutation is in the disordered N-terminal region proximal to important regulatory binding sites for phosphoinositides and for PACSIN3, which could lead to alterations in trafficking and/or channel sensitivity. Functional studies by western blot and immunohistochemical analysis show that p.S94L reduces TRPV4 protein stability because of increased cytotoxicity and therefore involves a gain-of-function mechanism.ConclusionThis study identifies a novel homozygous mutation in TRPV4 as a cause of the recessive form of congenital spinal muscular atrophy and arthrogryposis.

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