Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF

Khalil, Athar; Karroum, Samer Bou; Barake, Rana; Dunya, Gabriel; Abou-Rizk, Samer; Kamar, Amina; Nemer, Georges; Bassim, Marc K.

doi:10.1186/s12881-019-0942-4

Cited by 15 publications

(21 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients III:2 and IV:2 from family BD 35 and patients IV:1 and IV:3 from family ADRP 386 underwent diagnostic genetic testing by means of whole genome sequencing. Details of sequencing and variant classification have been described previously [ 52 ]. Segregation analysis in family members was performed using conventional Sanger sequencing.…”

Section: Methodsmentioning

confidence: 99%

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant

Kellner¹,

Weisschuh

Weinitz³

et al. 2021

IJMS

View full text Add to dashboard Cite

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.

show abstract

Section: Methodsmentioning

confidence: 99%

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant

Kellner¹,

Weisschuh

Weinitz³

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive neurodegenerative disorder found in several patients mainly in Finland [ 34 ]. Cases with middle-age-onset cerebellar ataxia were also reported which broaden the spectrum of pathogenic TWNK mutations [ 35 ]. Another TWNK -related disorder is a hepatocerebral mtDNA maintenance defect, severe multisystem syndrome.…”

Section: Discussionmentioning

confidence: 99%

Progressive External Ophthalmoplegia in Polish Patients—From Clinical Evaluation to Genetic Confirmation

Kierdaszuk

Kaliszewska

Rusecka

et al. 2020

Genes

View full text Add to dashboard Cite

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Clinical, electrophysiological, neuroradiological, and morphological data of 84 patients were analyzed. Genetic studies of mitochondrial DNA (mtDNA) were performed in all patients. Among nuclear DNA (nDNA) genes POLG was sequenced in 41 patients, TWNK (C10orf2) in 13 patients, and RNASEH1 in 2 patients. Total of 27 patients were included in the chronic progressive external ophthalmoplegia (CPEO) group, 24 in the CPEO+ group. Twenty-six patients had mitochondrial encephalomyopathy (ME), six patients Kearns–Sayre syndrome (KSS), and one patient sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic analysis of nDNA genes revealed the presence of pathogenic or possibly pathogenic variants in the POLG gene in nine patients, the TWNK gene in five patients and the RNASEH1 gene in two patients. Detailed patients’ history and careful assessment of family history are essential in the diagnostic work-up. Genetic studies of both mtDNA and nDNA are necessary for the final diagnosis of progressive external ophthalmoplegia and for genetic counseling.

show abstract

“…Studies using next-generation sequencing characterized a subgroup of DSRCT with secondary genomic alterations in genes associated with DNA damage repair (DDR), including ATM , RAD50 , BARD1 , BRCA1/2 , PALB2 and CHEK2 [ 19 , 103 ]. It is still unknown if those genomic alterations act as driver mutations in DSRCT tumorigenesis [ 103 ].…”

Section: Treatmentmentioning

confidence: 99%

“…c-Met (mesenchymal-epithelial transition factor) has been found to be overexpressed in a variety of solid tumors, including sarcomas [ 112 , 113 , 114 , 115 ], but the involvement of this receptor in DSRCT development is still scarce [ 100 ]. In the largest DSRCT comprehensive genomic profile study, no secondary mutation on c-MET was found [ 103 ]. There is a case report of a patient with intra-abdominal DSRCT who received anlotinib, a multi-kinase inhibitor that targets c-Met, for the progressive disease after surgery and first-line chemotherapy showing stable disease for 4 months [ 116 ].…”

Section: Treatmentmentioning

confidence: 99%

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Mello

Campos

Santos

et al. 2021

Cancers

View full text Add to dashboard Cite

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

show abstract

Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF

Cited by 15 publications

References 23 publications

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant

Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant

Progressive External Ophthalmoplegia in Polish Patients—From Clinical Evaluation to Genetic Confirmation

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Contact Info

Product

Resources

About