Novel Mutations in LRTOMT Associated With Moderate Progressive Hearing Loss in Autosomal Recessive Inheritance

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 142S-147S ◽  
Author(s):  
Aya Ichinose ◽  
Hideaki Moteki ◽  
Mitsuru Hattori ◽  
Shin-ya Nishio ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Autosomal Recessive Inheritance ◽  
Japanese Patients ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Coding Region ◽  
Novel Mutations ◽  
First Case

Objective: We present a patient who was identified with novel mutations in the LRTOMT gene and describe the clinical features of the phenotype including serial audiological findings. Methods: One hundred six Japanese patients with mild to moderate sensorineural hearing loss from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results: Compound heterozygotes with a novel frame-shift mutation and a missense mutation were identified in the LRTOMT gene. The mutated residues were segregated in both alleles of LRTOMT, present within the LRTOMT2 protein coding region. The patient had moderate sloping hearing loss at high frequencies, which progressed at 1000 Hz and higher frequencies over a period of 6 years. Conclusion: Hearing loss caused by mutations in the LRTOMT gene is extremely rare. This is the first case report of a compound heterozygous mutation in a nonconsanguineous family.

scholarly journals A novel compound heterozygous mutation in the GJB2 gene is associated with non-syndromic hearing loss in a Chinese family

2018 ◽  
Vol 12 (5) ◽  
pp. 470-475 ◽  
Author(s):  
Haiou Jiang ◽  
Youya Niu ◽  
Lingfeng Qu ◽  
Xueshuang Huang ◽  
Xinlong Zhu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Syndromic Hearing Loss ◽  
I Gene

scholarly journals Novel PTPRQ Mutations Identified in Three Congenital Hearing Loss Patients With Various Types of Hearing Loss

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 184S-192S ◽  
Author(s):  
Naoko Sakuma ◽  
Hideaki Moteki ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
Masahiro Takahashi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Manifestations ◽  
Vestibular Dysfunction ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Caloric Test ◽  
Compound Heterozygous ◽  
Site Mutation ◽  
Vestibular Evoked Myogenic Potential ◽  
Phenotypic Features

Objectives: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.

scholarly journals Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 135S-141S ◽  
Author(s):  
Kentaro Mori ◽  
Hideaki Moteki ◽  
Yumiko Kobayashi ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Genetic Modifier ◽  
Massively Parallel ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Congenital Hearing Loss ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Targeted Genomic Enrichment

Objective: We present 2 families that were identified with novel mutations in LOXHD1 as a cause of nonprogressive hearing loss. Methods: One thousand three hundred fourteen (1314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results: Two patients in 1 family affected with homozygous mutation c.879+1G>A in LOXHD1 showed profound congenital hearing loss, whereas 2 patients in another family with compound heterozygous mutations, c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X), showed moderate to severe hearing loss. Conclusion: Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences in phenotypes in each patient might be the result of the nature of the mutations or the location on the gene, or be influenced by a genetic modifier.

Novel Mutations in GRXCR1 at DFNB25 Lead to Progressive Hearing Loss and Dizziness

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 129S-134S ◽  
Author(s):  
Kentaro Mori ◽  
Ikuyo Miyanohara ◽  
Hideaki Moteki ◽  
Shin-ya Nishio ◽  
Yuichi Kurono ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Compound Heterozygous ◽  
Nonsyndromic Hearing Loss ◽  
Novel Mutations ◽  
Progressive Hearing Loss ◽  
Severe Hearing Loss ◽  
Parallel Sequencing ◽  
Targeted Genomic Enrichment

Objective: We identified 2 patients in 1 family who had novel mutations in GRXCR1, which caused progressive hearing loss. Methods: One thousand one hundred twenty Japanese hearing loss patients with sensorineural hearing loss from unrelated families were enrolled in this study. Targeted genomic enrichment with massively parallel sequencing of all known nonsyndromic hearing loss genes was used to identify the genetic causes of hearing loss. Results: In this study, 2 affected individuals with compound heterozygous mutations—c.439C>T (p.R147C) and c.784C>T (p.R262X)—in GRXCR1 were identified. The proband had moderate to severe hearing loss and suffered from dizziness with bilateral canal paralysis. Conclusion: Our cases are the first identified in the Japanese population and are consistent with previously reported cases. The frequency of mutations in GRXCR1 seems to be extremely rare. This study underscores the importance of using comprehensive genetic testing for hearing loss. Furthermore, longitudinal audiologic assessment and precise vestibular testing are necessary for a better understanding of the mechanisms of hearing loss and vestibular dysfunction caused by GRXCR1 mutations.

scholarly journals A Compound Heterozygous Mutation in the Ciliary Gene TTC21B Causes Nephronophthisis Type 12

2019 ◽  
Vol 09 (03) ◽  
pp. 198-202
Author(s):  
Wafaa Moustafa M. Abo El Fotoh ◽  
Amira Fathy Al-fiky
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Renal Disorder ◽  
Pathogenic Variants ◽  
Tubulointerstitial Lesions ◽  
Stage Renal Disease ◽  
End Stage

AbstractNephronophthisis (NPHP) is one of the renal ciliopathies and is also a cystic renal disorder with an autosomal recessive inheritance, which usually progresses to end-stage renal disease (ESRD). It affects children, adolescents, and young adults. In approximately 15% of cases, the features of a ciliopathy syndrome, which include liver fibrosis, skeletal anomalies, retinal abnormalities, and neurodevelopmental delay, will be present. We describe a case of a 2-year-old male child with ESRD on hemodialysis and a family record of a similar condition (his brother). The clinical features of this child are succinctly summarized. The genetic study was conducted using whole exome sequencing. TTC21B mutational variants were detected in our patient who exhibited nephrotic-range proteinuria, focal segmental glomerulosclerosis, and tubulointerstitial lesions that evolved to ESRD. Compound heterozygous mutations, c.626c > t (p.P209L) in exon 6 and c.450 g > a (p.W150Ter) in exon 5, were uncovered. These findings are in line with the description of autosomal recessive NPHP type 12. Both clinical and pathological diagnoses of NPHP are critical, bearing in mind ESRD as well as its related extrarenal defining features. Identification of the pathogenic variants in the TTC21B gene assisted in the successful proof of the clinical diagnosis NPHP12 as well as providing information for formal suitable prenatal counseling.

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