Analysis of candidate genes <i>ZEB1</i> and <i>LOXHD1</i> in late-onset Fuchs’ endothelial corneal dystrophy in an Indian cohort

Rao, B. Subba; Ansar, Samdani; Arokiasamy, Tharigopala; Sudhir, Rachapalli R.; Vetrivel, Umashankar; Rajagopal, Rama; Soumittra, Nagasamy

doi:10.1080/13816810.2018.1474367

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…However, in the four families we have studied, all the patients and the family members with normal hearing but carrying a single heterozygous mutation in the LOXHD1 gene showed no corneal abnormalities. Other studies also reported no symptoms of FCD were observed in the probands and their blood-related relatives [7,10,33]. Although the relationship of LOXHD1-related hearing loss and FCD is still unclear, we suggest that ophthalmologic examinations should be performed in patients with ARNSHL when LOXHD1 is suspected to be the pathogenic gene.…”

Section: Discussionmentioning

confidence: 61%

Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families

Bai

Zhang

et al. 2020

BioMed Research International

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Hearing loss is one of the most common sensory disorders in newborns and is mostly caused by genetic factors. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is usually characterized as a severe-to-profound congenital sensorineural hearing loss and later can cause various degrees of defect in the language and intelligent development of newborns. The mutations in LOXHD1 gene have been shown to cause DFNB77, a type of ARNSHL. To date, there are limited reports about the association between LOXHD1 gene and ARNSHL. In this study, we reported six patients from four Chinese families suffering from severe-to-profound nonsyndromic hearing loss. We performed targeted next generation sequencing in the six affected members and identified five novel pathogenic mutations in LOXHD1 including c.277G>A (p.D93N), c.611-2A>T, c.1255+3A>G, c.2329C>T (p.Q777∗), and c.5888delG (p.G1963Afs∗136). These mutations were confirmed to be cosegregated with the hearing impairment in the families by Sanger sequencing and were inherited in an autosomal recessive pattern. All of the five mutations were absent in 200 control subjects. There were no symptoms of Fuchs corneal dystrophy in the probands and their blood-related relatives. We concluded that these five novel mutations could be involved in the underlying mechanism resulting in the hearing loss, and this discovery expands the genotypic spectrum of LOXHD1 mutations.

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Section: Discussionmentioning

confidence: 61%

Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families

Bai

Zhang

et al. 2020

BioMed Research International

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“…Mutations in SLC4A11 contribute to approximately 11% and mutations in LOXHD1 contribute to 2% of the FECD cases in this study. A comparison of the role of ZEB1 across multiple ethnicities shows that the contribution of this gene in our Indian population is concurrent with other reports (Rao et al, 2018). In another study it was found that the single nucleotide polymorphisms (SNPs) of TCF4 gene, rs613872 and rs1759573 were associated with a higher risk of sporadic late‐onset FECD in Indian patients (Rao, Tharigopala, Rachapalli, Rajagopal, & Soumittra, 2017).…”

Section: Corneal Dystrophiessupporting

confidence: 92%

Ophthalmic genetics practice and research in India: Vision in 2020

Bansal

Tandon

Saxena

et al. 2020

American J of Med Genetics Pt C

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Ophthalmic genetics is a much needed and growing area in India. Ethnic diversity, with a high degree of consanguinity, has led to a high prevalence of genetic disorders in the country. As the second most populous country in the world, this naturally results in a significant number of affected people overall. Practice involves coherent association between ophthalmologists, genetic counselor and pediatricians. Eye genetics in India in recent times has witnessed advanced research using cutting edge diagnostics, next generation sequencing (NGS) approaches, stem cell therapies, gene therapy and genomic editing. This article will highlight the studies reporting genetic variations in the country, challenges in practice, and the latest advances in ophthalmic genetic research in India.

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“…In 2012, Riazuddin, et al first reported a heterozygous damaging variant within LOXHD1 in a multiplex family with dominant-inherited late-onset FCD [27]. However, subsequent studies failed to provide a strong association between LOXHD1 variants and FCD [20, 28–30]. Specially, results from a Chinese multi-generational FCD pedigree demonstrated that no pathogenic variants were identified in LOXHD1 [28].…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing identifies a novel missense variant within LOXHD1 causing rare hearing loss in a Chinese family

Shen

Wang

et al. 2019

BMC Med Genet

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BackgroundDeafness, autosomal recessive 77 (DFNB77) is a rare non-syndromic hearing loss (NSHL) worldwide, which is caused by deleterious variants within lipoxygenase homology domains 1 (LOXHD1). Here we identified that a novel missense variant of LOXHD1 was associated with NSHL in a Chinese family under consanguineous marriage.Case presentationA 28-year-old woman suffered a bilateral profound NSHL. Impedance audiometry, temporal bone computerized tomography (TBCT) scans and magnetic resonance imaging-inner ear hydrography (MRI-IEH) did not find any obvious abnormality of middle or inner ear. Routine genetic detection did not find pathogenic variants in common HL-associated genes. Therefore, we performed a whole-exome sequencing (WES) in this family. By trio-WES, co-segregation validation and bioinformatics analysis, we revealed that a novel homozygous variant in this patient, LOXHD1: c.5948C > T (p.S1983F), might be the pathogenic factor. Her parents (heterozygotes) and brother (wild-type) were asymptomatic.ConclusionsWe successfully identified a novel variant of LOXHD1 associated with a rare NSHL from a Chinese family. Our finds highlight the effectiveness of trio-WES for molecular diagnosis of rare NHSL, and expand the genotypic spectrum of DFNB77.Electronic supplementary materialThe online version of this article (10.1186/s12881-019-0758-2) contains supplementary material, which is available to authorized users.

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Analysis of candidate genes ZEB1 and LOXHD1 in late-onset Fuchs’ endothelial corneal dystrophy in an Indian cohort

Abstract: While mutations in ZEB1 contributed to 2% of the late-onset FECD cases, the exact role of the two VUS identified in ZEB1 and LOXHD1 in FECD pathogenesis needs to be studied.

Cited by 8 publications

References 25 publications

Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families

Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families

Ophthalmic genetics practice and research in India: Vision in 2020

Whole-exome sequencing identifies a novel missense variant within LOXHD1 causing rare hearing loss in a Chinese family

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