A novel variant in <i>DMXL2</i> gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family

Wonkam‐Tingang, Edmond; Schrauwen, Isabelle; Esoh, Kevin; Bharadwaj, Thashi; Nouel-Saied, Liz M; Acharya, Anushree; Nasır, Abdul; Leal, Suzanne M.; Wonkam, Ambroise

doi:10.1177/1535370221999746

Cited by 8 publications

(7 citation statements)

References 54 publications

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“…In fact, most of the familial cases reported in this study were seen in the Soninke ethnic group, which has a high tendency for consanguineous marriage. In Mali, as in numerous understudied African populations, it is probable that numerous variants of known and potentially novel genes remain to be discovered ( 37 – 39 ). Among cases with a suspected genetic origin, we identified two families with WS, the most common SHI reported in some countries ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali

et al. 2021

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Objectives: To identify the etiologies of hearing impairment (HI) in schools for students who are deaf and to use a systematic review to summarize reports on the etiologies and clinical and genetic features of HI in Mali.Methods: We included individuals with HI that started before the age of 15 years old. Patients were carefully evaluated under standard practices, and pure-tone audiometry was performed where possible. We then searched for articles published on HI in the Malian population from the databases' inception to March 30, 2020.Results: A total of 117 individuals from two schools for the deaf were included, and a male predominance (sex ratio 1.3; 65/52) was noted. HI was pre-lingual in 82.2% (n = 117), and the median age at diagnosis was 12 years old. The etiologies were environmental in 59.4% (70/117), with meningitis being the leading cause (40%, 20/70), followed by cases with genetic suspicion (29.3%, 21/117). In 11.3% (8/117) of patients, no etiology was identified. Among cases with genetic suspicion, three were syndromic, including two cases of Waardenburg syndrome, while 15 individuals had non-syndromic HI. An autosomal recessive inheritance pattern was observed in 83.3% of families (15/18), and consanguinity was reported in 55.5% (10/18) of putative genetic cases.Conclusion: This study concludes that environmental factors are the leading causes of HI in Mali. However, genetic causes should be investigated, particularly in the context of a population with a high consanguinity rate.

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Section: Discussionmentioning

confidence: 99%

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali

et al. 2021

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“…DMXL2: DMXL2 (MIM 612186; 15q21.2) was recently identified to have missense variants causing AD nonsyndromic hearing loss in Chinese and Cameroonian families [64,65]. In these families, the affected individuals were mostly adult with progressive hearing loss and no reported temporal bone abnormalities, although one Cameroonian child had congenital profound hearing loss [65]. Our patient ID5 has a novel heterozygous DMXL2 variant c.257T>C (p.(Leu86Ser)) (Table 2).…”

Section: Resultsmentioning

confidence: 85%

“…This case shows potential overlap of clinical presentation due to multiple deleterious variants, of which the LMX1A variant is the strongest etiology of inner ear abnormalities in this patient while the ZFHX4 or ARHGAP4 variants may explain ID3 s developmental delay. DMXL2: DMXL2 (MIM 612186; 15q21.2) was recently identified to have missense variants causing AD nonsyndromic hearing loss in Chinese and Cameroonian families [64,65]. In these families, the affected individuals were mostly adult with progressive hearing loss and no reported temporal bone abnormalities, although one Cameroonian child had congenital profound hearing loss [65].…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies

Santos‐Cortez

Yarza

Bootpetch

et al. 2021

Genes

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Background: Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Methods: Clinical and exome data from 15 children with hearing loss were reviewed. Standard tools for annotating variants were used and rare, putatively deleterious variants were selected from the exome data. Results: In 15 children, 21 rare damaging variants in 17 genes were identified, including: 14 known hearing loss or neurodevelopmental genes, 11 of which had novel variants; and three candidate genes IST1, CBLN3 and GDPD5, two of which were identified in children with both hearing loss and enlarged vestibular aqueducts. Patients with variants within IST1 and MYO18B had poorer outcomes after cochlear implantation. Conclusion: Our findings highlight the importance of identifying novel variants and genes in ethnic groups that are understudied for hearing loss.

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“…The association of RC3α/DMXL2 with human diseases, e.g., Ohtahara syndrome (a syndromic deafness-associated disease with mutations in the RC3α/DMXL2 gene) and some non-syndromic hearing losses with sensorineural impairment [ 96 , 97 , 98 ], emphasizes the importance to further explore its function at ribbon synapses, including ribbon synapses of the retina.…”

Section: Discussionmentioning

confidence: 99%

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Dittrich

Ramesh

Jung

et al. 2023

Cells

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Ribbon synapses reliably transmit synaptic signals over a broad signalling range. Rod photoreceptor ribbon synapses are capable of transmitting signals generated by the absorption of single photons. The high precision of ribbon synapses emphasizes the need for particularly efficient signalling mechanisms. Synaptic ribbons are presynaptic specializations of ribbon synapses and are anchored to the active zone. Synaptic ribbons bind many synaptic vesicles that are delivered to the active zone for continuous and faithful signalling. In the present study we demonstrate with independent antibodies at the light- and electron microscopic level that rabconnectin-3α (RC3α)—alternative name Dmx-like 2 (DMXL2)—is localized to the synaptic ribbons of rod photoreceptor synapses in the mouse retina. In the brain, RC3α-containing complexes are known to interact with important components of synaptic vesicles, including Rab3-activating/inactivating enzymes, priming proteins and the vesicular H+-ATPase that acidifies the synaptic vesicle lumen to promote full neurotransmitter loading. The association of RC3α/DMXL2 with rod synaptic ribbons of the mouse retina could enable these structures to deliver only fully signalling-competent synaptic vesicles to the active zone thus contributing to reliable synaptic communication.

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A novel variant in DMXL2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family

Cited by 8 publications

References 54 publications

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali

Etiologies of Childhood Hearing Impairment in Schools for the Deaf in Mali

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

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