scholarly journals A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole‐exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome

2020 ◽  
Vol 8 (6) ◽  
Author(s):  
Xuechao Zhao ◽  
Yanhong Wang ◽  
Shiyue Mei ◽  
Xiangdong Kong
Keyword(s):  
Mental Retardation ◽  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Chinese Family ◽  
Whole Exome

scholarly journals A Novel BBS9 Mutation Identified via Whole-Exome Sequencing in a Chinese Family with Bardet-Biedl Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yue Zhang ◽  
Manhong Xu ◽  
Minglian Zhang ◽  
Guoxing Yang ◽  
Xiaorong Li
Keyword(s):  
Mental Retardation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Cone Dystrophy ◽  
Bardet Biedl Syndrome ◽  
Homozygous Variant ◽  
Whole Exome

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by polydactyly, obesity, rod-cone dystrophy, and mental retardation. Twenty-one genes have been identified as causing BBS. This study collected a BBS pedigree from two patients and performed whole-exome sequencing on one patient. We identified a novel homozygous variant c.1114C>T (p.Q372X) in the BBS9 of the two siblings. This variant was confirmed and completely cosegregated with the disease of this family by Sanger sequencing. We report a novel homozygous variant c.1114C>T in the BBS9 gene in a Chinese family.

Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia

2018 ◽  
Vol 28 (5) ◽  
pp. 688-691 ◽  
Author(s):  
Hao Huang ◽  
Dong-Bo Ding ◽  
Liang-Liang Fan ◽  
Jie-Yuan Jin ◽  
Jing-Jing Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Chinese Family ◽  
Illumina Hiseq ◽  
Α Subunit ◽  
Pathogenic Genes ◽  
Whole Exome ◽  
Gene Filtering ◽  
Protein Dysfunction

AbstractBackgroundSCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.MethodsGenomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.Results and conclusionsA novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.

scholarly journals Novel SOX2 Mutation in Autosomal Dominant Cataract-Microcornea Syndrome

2021 ◽  
Author(s):  
Zhi-Bo Lin ◽  
Jin Li ◽  
Hai-Sen Sun ◽  
A-Yong Yu ◽  
Shi-Hao Chen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
High Mobility ◽  
Chinese Family ◽  
Whole Exome

Abstract Background: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. Purpose: To unravel the genetic cause of autosomal dominant family with CCMC.Methods: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. Results: Four CCMC patients from a Chinese family, and five unaffected family members were enrolled in this study. Using whole-exome sequencing, missense mutation c.295G>T (p.a99s, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level.Conclusions: A novel missense mutation (c.295G>T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study firstly determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

Inherited GPI-Anchor Deficiencies Caused By The Hypomorphic Mutations In PIG A gene: Comparison To Paroxysmal Nocturnal Hemogrobinuria

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3701-3701
Author(s):  
Yoshiko Murakami ◽  
Mitsuhiro Kato ◽  
Hirotomo Saitsu ◽  
Kenjiro Kikuchi ◽  
Shuei Watanabe ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Intellectual Disabilities ◽  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Nonsense Mutation ◽  
The Other ◽  
Facs Analysis ◽  
Whole Exome ◽  
Partial Deficiency

Abstract Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors 150 or more kinds of proteins to the cell surface. There are at least 26 genes involved in the biosynthesis and transport of GPI anchored proteins (GPI-APs). In paroxysmal nocturnal hemogrobinuria (PNH), an acquired GPI deficiency, somatic mutation in X-linked PIGA accounts for most of the patients. A case with PNH due to a combination of inherited mutation in one allele and a somatic mutation in the other allele of autosomal gene PIGT was reported recently (Blood 2013 doi:10.1182/blood-2013-01-481499). On the other hand, many inherited GPI deficiencies (IGDs) were found recently using whole exome sequencing (Nat Genet 2010 vol.42 p827, Am J Hum Genet 2012 vol. 90 p295, p146, Am J Hum Genet 2012 vol. 91 p146, Am J Hum Genet 2013 vol. 92 p584). As the complete GPI deficiency causes embryonic death, these patients with IGD are partial deficiency. The major symptoms of IGDs include mental retardation, epilepsy, coarse facial features and multiple organ anomalies that vary in severity depending upon the degree of defect and/or position in the pathway of affected gene. We clarified a mechanism of hyperphosphatasia, an elevated release of tissue nonspecific alkaline phosphatase (TNAP, GPI-AP), seen in some of the patients with IGDs such as hyperphosphatasia mental retardation syndrome or Mabry syndrome caused by mutation in genes in the later stage of GPI biosynthesis (J Biol Chem. 2012 vol. 287 p6318) Here, we report four male patients with intellectual disabilities accompanied by seizures caused by the mutations in PIGA gene. These mutations were found by whole-exome sequencing using the Illumina HiSeq system. PIGA is X-linked gene which is involved in the first step of GPI biosynthesis pathway. These patients have germline hypomorphic mutations in PIGAgene and have completely different symptoms from patients with PNH, which is characterized by complement-mediated intravascular hemolysis. Patient 1 had a hemizygous nonsense mutation, and was diagnosed with Ohtahara syndrome (early infantile epileptic encephalopathy with suppression burst) with multiple congenital anomalies. The nonsense mutation is leaky and caused a partial deficiency. Patient 2 had a maternally inherited hemizygous missense mutation and was diagnosed with early-onset West syndrome (a severe epilepsy syndrome characterized by infantile spasm with hypsarrhythmia). Patients 3 and 4 are brothers, had maternally inherited hemizygous missense mutation and were suffering from severe intellectual disabilities with seizures but not with any anomalies. Analysis by flow cytometry of patients’ blood cells revealed that all four patients showed decreased expression of GPI-APs on the granulocytes but not in erythrocytes or lymphocytes, suggesting that FACS analysis of granulocytes is useful to screen patients with IGD. Interestingly, the FACS analysis of the granulocytes from the mother of patients 3 and 4 showed mosaic pattern in CD16 expression. The mother seemed to have no neurological symptom, raising the possibility that contribution of GPI-AP-deficient cells to neuronal system does not occur or is only limited. Although PNH and IGDs are different diseases, both are partial GPI deficiencies, the former affecting only hematopoietic cells, the latter having the hypomorphic mutations, which rescue the patients from lethality but cause the severe hematopoietic and developmental abnormalities, respectively. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

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