Identification of Two Novel Compound Heterozygous PTPRQ Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family
Xue Gao,Yu Su,Yulan Chen,Mingyu Han,Yongyi Yuan,Jin-Cao Xu,Feng Xin,Mei-Guang Zhang,Shasha Huang,Guojian Wang,Dongyang Kang,Liping Guan,Jianguo Zhang,Pu Dai +13 more
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TL;DR: Heterozygosity for c.
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Abstract: Mutations in PTPRQ are associated with deafness in humans due to defects of stereocilia in hair cells. Using whole exome sequencing, we identified responsible gene of family 1572 with autosomal recessively non-syndromic hearing loss (ARNSHL). We also used DNA from 74 familial patients with ARNSHL and 656 ethnically matched control chromosomes to perform extended variant analysis. We identified two novel compound heterozygous missense mutations, c. 3125 A>G p.D1042G (maternal allele) and c.5981 A>G p.E1994G (paternal allele), in the PTPRQ gene, as the cause of recessively inherited sensorineural hearing loss in family 1572. Both variants co-segregated with hearing loss phenotype in family 1572, but were absent in 74 familial patients. Heterozygosity for c. 3125 A>G was identified in two samples from unaffected Chinese individuals (656 chromosomes). Therefore, the hearing loss in this family was caused by two novel compound heterozygous mutations in PTPRQ.
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Genetic causes of moderate to severe hearing loss point to modifiers.
Sadaf Naz,Ayesha Imtiaz,Ghulam Mujtaba,Azra Maqsood,Rasheeda Bashir,Ihtisham Bukhari,Muhammad Riaz Khan,Memoona Ramzan,Amara Fatima,Atteeq U. Rehman,Muddassar Iqbal,Taimur Chaudhry,Merete Lund,Carmen C. Brewer,Robert J. Morell,Thomas B. Friedman +15 more
TL;DR: The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness, and data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity.
First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene.
Dominika Oziębło,Anna Sarosiak,Marcin L. Leja,Birgit Budde,Grażyna Tacikowska,Nataliya Di Donato,Hanno J. Bolz,Peter Nürnberg,Henryk Skarżyński,Monika Ołdak +9 more
TL;DR: Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction, which strongly reinforces the inclusion ofPTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.
Identification of Novel PTPRQ and MYO1A Mutations in An Iranian Pedigree with Autosomal Recessive Hearing Loss.
TL;DR: The results suggest that the homozygous PTPRQ variant maybe the pathogenic variant for ARNSHL due to the recessive nature of the disorder, and the heterozygous MYO1A may also be involved in this disorder due to its multigenic pattern.
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Autosomal Recessive Congenital Sensorineural Hearing Loss due to a Novel Compound Heterozygous PTPRQ Mutation in a Chinese Family
Xia Wu,Shan Wang,Sen Chen,Ying-ying Wen,Bo Liu,Wen Xie,Dan Li,Lin Liu,Xiang Huang,Yu Sun,Weijia Kong +10 more
TL;DR: Using next-generation sequencing and Sanger sequencing method, a novel compound heterozygous missense mutation is identified, c.4472C>T p.1973T>C p.V658A, in PTPRQ gene, the first reported to be the cause of recessively inherited sensorineural hearing loss.
A systematic review of the monogenic causes of Non‐Syndromic Hearing Loss (NSHL) and discussion of Current Diagnosis and Treatment options
TL;DR: Overall, pathogenic variants in 98 different genes have been associated with NSHL, and these genes have important role to play during early embryonic development in ear structure formation and hearing development.
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References
Newborn Hearing Screening — A Silent Revolution
TL;DR: The implementation of universal screening programs to detect hearing defects in newborns has dramatically increased the identification of hearing loss in infants, and further improvement in these programs can readily be achieved.
Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces
TL;DR: HOPE is described, a fully automatic program that analyzes the structural and functional effects of point mutations and builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers.
Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss
Christopher J. Klein,Maria Victoria Botuyan,Yanhong Wu,Christopher J. Ward,Garth A. Nicholson,Simon Hammans,Kaori Hojo,Hiromitch Yamanishi,Adam R. Karpf,Douglas C. Wallace,Mariella Simon,Cecilie M. Lander,Lisa A. Boardman,Julie M. Cunningham,Glenn E. Smith,William J. Litchy,Benjamin Boes,Elizabeth J. Atkinson,Sumit Middha,P. James B. Dyck,Joseph E. Parisi,Georges Mer,David I. Smith,Peter J. Dyck +23 more
TL;DR: These mutations cause premature degradation of mutant proteins, reduced methyltransferase activity and impaired heterochromatin binding during the G2 cell cycle phase leading to global hypomethylation and site-specific hypermethylation.
Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome
Sarah B. Pierce,Karen M. Chisholm,Eric D. Lynch,Ming K. Lee,Tom Walsh,John M. Opitz,Weiqing Li,Rachel E. Klevit,Mary Claire King +8 more
TL;DR: The relationship between HARS2 and Perrault syndrome illustrates how causality may be demonstrated for extremely rare inherited mutations in essential, highly conserved genes.
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Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome
Sarah B. Pierce,Tom Walsh,Karen M. Chisholm,Ming K. Lee,Anne M. Thornton,Agata Fiumara,John M. Opitz,Ephrat Levy-Lahad,Ephrat Levy-Lahad,Rachel E. Klevit,Mary Claire King +10 more
TL;DR: Whole-exome sequencing of genomic DNA from two sisters with well-characterized Perrault syndrome revealed exactly one gene with two rare functional variants: HSD17B4, which encodes 17beta-hydroxysteroid dehydrogenase type 4 (HSD 17B4), also known as D-bifunctional protein (DBP), a multifunctional peroxisomal enzyme involved in fatty acid beta-oxidation and steroid metabolism.
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