DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature

Sorrentino, Ugo; Piccolo, C.; Rigon, Chiara; Brasson, Valeria; Trevisson, Eva; Boaretto, Francesca; Martini, Alessandro; Cassina, Matteo

doi:10.3390/audiolres11040052

Cited by 6 publications

(6 citation statements)

References 65 publications

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“…Most variants in the ACTG1 gene have isolated HL. In syndromic cases, the other reported alterations are cleft-lip/palate in the variant c.94C > T, dysmorphic features in the variants c.617G > A p.(Arg206Gln),c.1003C > T; p.(Arg335Cys), eye problems in the variants c.625G > A (p. Val209Met) and p.Ala58Val, cardiac abnormalities in c.617G > A p.(Arg206Gln) and c.1003C > T; p.(Arg335Cys) variants and psychomotor delay associated with microcephaly and short stature in the c.617G > A p.(Arg206Gln) variant [ 9 , 25 , 26 , 27 , 28 ]. In the work by Chacon-Camacho et al, clinical features such as eye malformations, dysmorphic facial features, and psychomotor delay in the variant c.176A > G, p.Gln59Arg and eyes and genital anomalies, facial dysmorphism, psychomotor delay and encephalic alterations at MRI in c.608C > T, p.Thr203Met variant are described [ 29 ].…”

Section: Hearing Loss In Baraitser–winter Syndrome: Evidence Synthesismentioning

confidence: 99%

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Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Ghiselli,

Parmeggiani,

Zambonini

et al. 2024

JCM

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Background: Baraitser–Winter Syndrome (BRWS) is a rare autosomal dominant condition associated with hearing loss (HL). In the literature, two types of this condition are reported, Baraitser–Winter type 1 (BRWS1) and type 2 (BRWS2) produced by specific pathogenetic variants of two different genes, ACTB for BRWS1 and ACTG1 for BRWS2. In addition to syndromic BRWS2, some pathogenic variants in ACTG1 are associated also to another pathologic entity, the “Autosomal dominant non-syndromic hearing loss 20/26”. In these syndromes, typical craniofacial features, sensory impairment (vision and hearing) and intellectual disabilities are frequently present. Heart anomalies, renal and gastrointestinal involvement and seizure are also common. Wide inter- and intra-familial variety in the phenotypic spectrum is reported. Some phenotypic aspects of these syndromes are not yet fully described, such as the degree and progression of HL, and better knowledge of them could be useful for correct follow-up and treatment. Methods and Results: In this study, we report two cases of children with HL and diagnosis of BRWS and a review of the current literature on HL in these syndromes.

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Section: Hearing Loss In Baraitser–winter Syndrome: Evidence Synthesismentioning

confidence: 99%

“…In some cases, intellectual disability, seizures, heart defects, renal and gastrointestinal malformations and cleft lip palate occur. The concomitant presence of sensorineural hearing loss (SNHL) has been described, but the characteristics of this deficit are poorly described [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Ghiselli,

Parmeggiani,

Zambonini

et al. 2024

JCM

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“…Autosomal dominant non-syndromic sensorineural deafness 20/26 (DFNA20/26) is caused by heterozygous mutations in the ACTG1 gene on chromosome 17q25 [ 11 ]. Mutations in the ACTG1 gene can be associated with autosomal dominant non-syndromic HL (DFNA20/26) and Baraitser–Winter syndrome (a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies, and intellectual disability) [ 11 , 173 ]. The ACTG1 gene encodes gamma actin, which is a major actin protein in the cytoskeleton of auditory hair cells and is essential for the maintenance of stereocilia [ 173 ].…”

Section: Autosomal Dominant Non-syndromic Hearing Loss (Dfna)mentioning

confidence: 99%

“…Mutations in the ACTG1 gene can be associated with autosomal dominant non-syndromic HL (DFNA20/26) and Baraitser–Winter syndrome (a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies, and intellectual disability) [ 11 , 173 ]. The ACTG1 gene encodes gamma actin, which is a major actin protein in the cytoskeleton of auditory hair cells and is essential for the maintenance of stereocilia [ 173 ]. In Europe, DFNA20/26 was reported in Dutch [ 51 , 174 , 175 ], Norwegian [ 176 ], Spanish [ 177 ], and Italian [ 173 ] families.…”

Section: Autosomal Dominant Non-syndromic Hearing Loss (Dfna)mentioning

confidence: 99%

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

et al. 2023

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Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants.

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“…In the literature to date, these variants do not overlap with the 17/51 confirmed B-WS-related ACTG1 variants [ 53 ]. The two conditions are therefore considered to be separate molecular and clinical diagnoses.…”

Section: Introductionmentioning

confidence: 99%

De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser–Winter Syndrome

Dawidziuk¹,

Kutkowska-Kaźmierczak²,

Bukowska‐Olech

et al. 2022

IJMS

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Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser–Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (β-actin) or ACTG1 (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated γ-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20/26 deafness, representing phenotypic expansion. The patient’s exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that γ-actin c.542C > T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.

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DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature

Cited by 6 publications

References 65 publications

Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Hearing Loss in Baraitser–Winter Syndrome: Case Reports and Review of the Literature

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser–Winter Syndrome

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