scholarly journals Novel TRAPPC11 Mutations in a Chinese Pedigree of Limb Girdle Muscular Dystrophy

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xike Wang ◽  
Yue Wu ◽  
Yuxia Cui ◽  
Nan Wang ◽  
Lasse Folkersen ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Muscular Dystrophies ◽  
Heterozygous Mutation ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Double Mutation ◽  
Whole Exome ◽  
Genes Encoding ◽  
Mode Of Transmission ◽  
Dystrophin Complex

Limb girdle muscular dystrophies (LGMDs) are a heterogeneous group of genetic myopathies leading primarily to proximal muscle weakness. It is caused by mutations at over 50 known genetic loci typically from mutations in genes encoding constituents of the sarcolemmal dystrophin complex or related functions. Herein we describe the case of two siblings with LGMD that were investigated using whole-exome sequencing followed by Sanger sequencing validation of a specific double-mutation in the TRAPPC11 gene. Further, from parental sequencing we determined the mode of transmission, a double heterozygous mutation at the maternal and paternal alleles. The two mutations detected have not been described in other patients.

scholarly journals Digenic Variants in the TTN and TRAPPC11 Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family

2021 ◽  
Vol 15 ◽  
Author(s):  
Qian Chen ◽  
Wen Zheng ◽  
Hongbo Xu ◽  
Yan Yang ◽  
Zhi Song ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Genetic Disorders ◽  
Muscular Dystrophies ◽  
Chinese Family ◽  
Disease Phenotype ◽  
Proximal Muscle ◽  
Whole Exome ◽  
The Family ◽  
Protein Particle ◽  
Muscle Impairment

Limb-girdle muscular dystrophies (LGMD) are hereditary genetic disorders characterized by progressive muscle impairment which predominantly include proximal muscle weaknesses in the pelvic and shoulder girdles. This article describes an attempt to identify genetic cause(s) for a LGMD pedigree via a combination of whole exome sequencing and Sanger sequencing. Digenic variants, the titin gene (TTN) c.19481T>G (p.Leu6494Arg) and the trafficking protein particle complex 11 gene (TRAPPC11) c.3092C>G (p.Pro1031Arg), co-segregated with the disease phenotype in the family, suggesting their possible pathogenicity.

scholarly journals Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Qin Xiang ◽  
Lamei Yuan ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yunfeiyang Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Transforming Growth Factor ◽  
Corneal Dystrophy ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Type I ◽  
Whole Exome ◽  
The Family

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

Identification of Dido1 Mutation Associated with Familial Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 169-169 ◽  
Author(s):  
Naomi Galili ◽  
Vladimir Trifonov ◽  
Mark Ewalt ◽  
Siddhartha Mukherjee ◽  
Raul Rabadan ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Genetic Alterations ◽  
Normal Male ◽  
Heterozygous Mutation ◽  
Hematopoietic Stem ◽  
Synonymous Mutations ◽  
Whole Exome ◽  
Putative Transcription Factor

Abstract Abstract 169 Introduction Approximately half of all patients with sporadic MDS will present with one of the known recurrent genetic alterations including additions/deletions of large chromosomal segments or mutations in single genes. Familial cases of MDS are rare, however, and the mutations that have been identified are not unique to MDS. Here we describe a family in which three of nine siblings were affected with early-onset MDS and a del(20) karyotype (Table 1). One of the brothers progressed to AML and died while the remaining 2 brothers are stable. Methods and Results We performed whole exome sequencing on 2 affected brothers and 2 normal male family members followed by Sanger sequencing. Comparison of non-synonymous mutations common to the 2 brothers with MDS but not found in the normal controls revealed a mutated gene, Dido1, which is located at 20q13.33 upstream of the deleted region in the MDS brothers. The G to A mutation leads to substitution of a bulky basic, polar arginine in place of a small neutral non-polar glycine at amino acid 956 of the protein. This mutation, confirmed by PCR, was present in one allele in both the marrow and T-cells (not part of the MDS clone) of both brothers with MDS (Figure 1) showing that the mutation is not somatic but is, rather, a germline mutation. Since all three affected brothers harbored a del(20), it was of interest to investigate whether other patients with MDS or MDS/MPD and del(20)(q11.2) may also have this specific mutation. DNA from bone marrow mononuclear cells (BMMNC) of 10 del(20q) patients with either MDS or MDS/MPD was examined by PCR and Sanger sequencing. No mutation was found in any of the samples, suggesting that the mutation is unique to the affected family. BMMNC were available for 16 additional members of this extensive family. PCR followed by sequencing showed that 7/16 members of generation III have the identical heterozygous mutation. Interestingly, while no DNA was available from the brother who died of AML, analysis of his children revealed that 2 sons (III- Q and III-R) carry the mutation, confirming that the father also carried this mutation. Similarly, while DNA from sister II-G was not available for analysis, one of her daughters carries the mutation confirming the presence of mutation in the mother. Discussion Death inducer-obliterator 1 (Dido1) is a putative transcription factor originally identified in a screen for apoptosis related genes in a murine pre-B cell line. The gene encodes three alternate isoforms and gene targeting of all three isoforms in a murine model leads to development of a transplantable myeloid disorder with features similar to MDS/MPN. These studies also showed variable decreased Dido1 expression in a subset of patients with myeloid disorders when compared to healthy controls. Our results support the hypothesis that Dido1 aberrations in hematopoietic stem cells may contribute to MDS evolution. The fact that deletions in the long arm of chromosome 20 are one of the most frequent aberrations found in MDS and clearly was a secondary event in the 3 affected brothers of this family suggests that Dido1 may ontribute to this specific genomic instability. Generation III are still young, but those with the mutation may have an increased susceptibility to myeloid disease and should be clinically followed. Conclusion The identification of the Dido1 mutation in this family suggests a novel pathogenic mechanism for the development of familial MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guangxian Yang ◽  
Yi Yin ◽  
Zhiping Tan ◽  
Jian Liu ◽  
Xicheng Deng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

scholarly journals Sarcoglycanopathy - a rare case report and literature review

2015 ◽  
Vol 22 (2) ◽  
pp. 232-235
Author(s):  
Ekramul Mustafa ◽  
Md Azizul Hasan Khandaker ◽  
Md Mamunur Rashid ◽  
Swapon Kumar Ghose ◽  
Masood Salehin ◽  
...  
Keyword(s):  
Rare Case ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Muscular Dystrophies ◽  
Recessive Inheritance ◽  
Rare Entity ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Medical College ◽  
Rare Case Report

Sarcoglycanopathies are relatively rare progressive muscular dystrophies with autosomal recessive inheritance designated as á, â, ã, or ä sarcoglycanopath.; which belong to the group of limb girdle muscular dystrophies and are caused by mutations in any of the four sarcoglycan genes: alpha (LGMD 2D), beta (LGMD 2E), gamma (LGMD 2C) and delta (LGMD 2F). The phenotype resembles dystrophinopathies due to proximal muscle weakness and calf hypertrophy. Reports from Bangladesh are scarce. We report a rare case of primary sarcoglycanopathy (SGP) which emphasizes the evolving concept of “dystrophinopathy to sarco-glycanopathy”. and describe literature pertaining to this rare entity DOI: http://dx.doi.org/10.3329/jdmc.v22i2.21551 J Dhaka Medical College, Vol. 22, No.2, October, 2013, Page 232-235

scholarly journals Sarcoglycanopathy - A Rare Case Report and Literature Review

2014 ◽  
Vol 15 (1) ◽  
pp. 77-79
Author(s):  
Ekramul Mustafa ◽  
Md. Azizul Hasan Khandaker ◽  
Md. Mamunur Rashid ◽  
Swapon Kumar Ghose ◽  
Mostofa Kamal Chowdhury
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Rare Case ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Muscular Dystrophies ◽  
Recessive Inheritance ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Rare Case Report

Sarcoglycanopathies are relatively rare progressive muscular dystrophies with autosomal recessive inheritance designated as a, b, g, or d sarcoglycanopath.; which belong to the group of limb girdle muscular dystrophies (LGMD) and are caused by mutations in any of the four sarcoglycan genes: alpha (LGMD 2D), beta (LGMD 2E), gamma (LGMD 2C) and delta (LGMD 2F). The phenotype resembles dystrophinopathies due to proximal muscle weakness and calf hypertrophy. Reports from Bangladesh are scarce. We report a rare case of primary sarcoglycanopathy (SGP) which emphasizes the evolving concept of “dystrophinopathy to sarco-glycanopathy” and describe literature pertaining to this rare entity.DOI: http://dx.doi.org/10.3329/jom.v15i1.19880 J Medicine 2014; 15: 77-79

scholarly journals Two Novel Homozygous HPS6 Mutations (Double Mutant) Identified by Whole-Exome Sequencing in a Saudi Consanguineous Family Suspected for Oculocutaneous Albinism

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 14
Author(s):  
Sajjad Karim ◽  
Samah Saharti ◽  
Nofe Alganmi ◽  
Zeenat Mirza ◽  
Ahmed Alfares ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Autosomal Recessive Disorder ◽  
Bioinformatic Analysis ◽  
Oculocutaneous Albinism ◽  
Double Mutation ◽  
Pathogenic Variants ◽  
Whole Exome

Background: Oculocutaneous albinism (OCA) is an autosomal recessive disorder of low or missing pigmentation in the eyes, hair, and skin. Multiple types of OCA, including Hermansky-Pudlak syndrome 6 (HPS6), are distinguished by their genetic cause and pigmentation pattern. HPS6 is characterized by OCA, nose bleeding due to platelet dysfunction, and lysosome storage defect. To date, 25 disease-associated mutations have been reported in the HPS6 gene. Methods: DNA was extracted from proband, and whole-exome sequencing (WES) was performed using the Illumina NovaSeq platform. Bioinformatic analysis was done with a custom-designed filter pipeline to detect the causative variant. We did Sanger sequencing to confirm the candidate variant and segregation analysis, and protein-based structural analysis to evaluate the functional impact of variants. Result: Proband-based WES identified two novel homozygous mutations in HPS6 (double mutation, c.1136C>A and c.1789delG) in an OCA suspect. Sanger sequencing confirmed the WES results. Although no platelet and/or lysosome storage defect was detected in the patient or family, an oculocutaneous albinism diagnosis was established based on the HPS6 mutations. Structural analysis revealed the transformation of abnormalities at protein level for both nonsense and frameshift mutations in HPS6. Conclusion: To the best of our knowledge, the double mutation in HPS6 (p.Ser379Ter and p.Ala597GlnfsTer16) represents novel pathogenic variants, not described previously, which we report for the first time in the Saudi family. In silico analyses showed a significant impact on protein structure. WES should be used to identify HPS6 and/or other disease-associated genetic variants in Saudi Arabia, particularly in consanguineous families.

MRI FINDINGS IN IDIOPATHIC GLUTEAL FIBROSIS

2011 ◽  
Vol 14 (02) ◽  
pp. 1272001
Author(s):  
Ravi Kanth Jakkani ◽  
Jyoti Sureka ◽  
Sanuj Panwar ◽  
S. Shyam
Keyword(s):  
Muscle Weakness ◽  
Muscular Dystrophies ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Mri Findings ◽  
Intramuscular Injections ◽  
Gluteal Fibrosis

Gluteal fibrosis is usually secondary to intramuscular injections and rarely can be idiopathic in nature. Clinically characterized by proximal muscle weakness and in advanced cases groove can be seen in gluteal regions. It can mimic with other conditions like muscular dystrophies and poliomyelitis. MRI is a very valuable tool in diagnosing this disorder and is also helpful to exclude other conditions.

scholarly journals Whole-exome Sequencing Identified a Novel Heterozygous Mutation of SALL1 and a New Homozygous Mutation of PTPRQ in a Chinese Family With Townes-brocks Syndrome and Hearing Loss

2021 ◽  
Author(s):  
Yang Guangxian ◽  
Yin Yi ◽  
Tan Zhiping ◽  
Liu Jian ◽  
Deng Xicheng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease (CHD). In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns.Methods: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss.Results: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation (ENST00000266688: c.1057_1057delC, p. L353SfsX8)) of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis.Conclusions: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

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