Progressive macrothrombocytopenia and hearing loss in a large family with DIAPH1 related disease.

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Progressive macrothrombocytopenia and hearing loss in a large family with DIAPH1 related disease.

Am J Med Genet A. 2017 Aug 16;:

Authors: Ganaha A, Kaname T, Shinjou A, Chinen Y, Yanagi K, Higa T, Kondo S, Suzuki M

Abstract
In this study, we describe a Japanese family with progressive hearing loss and macrothrombocytopenia. Using next-generation and Sanger sequencing analyses, we identified a heterozygous variant in exon 27 of the DIAPH1 gene (NM_005219), c.3637C>T, p.R1213X. All patients in the family had sensorineural hearing loss and macrothrombocytopenia. None of the patients exhibited a tendency to bleed. No pathogenic variants were found in the MYH9 gene. Hearing loss began with high-frequency loss during early childhood and progressed to severe hearing loss involving all frequencies. Analyses of the mean platelet volume and platelet distribution width indicated that the macrothrombocytopenia is progressive in patients with DIAPH1 related disease.There are no reports describing progressive macrothrombocytopenia in patients with pathogenic variants of DIAPH1. Thus, progressive macrothrombocytopenia may be a novel feature of deafness patients with pathogenic variants in DIAPH1.

PMID: 28815995 [PubMed - as supplied by publisher]

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SLC52A3, A Brown-Vialetto-van Laere syndrome candidate gene is essential for mouse development, but dispensable for motor neuron differentiation.

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SLC52A3, A Brown-Vialetto-van Laere syndrome candidate gene is essential for mouse development, but dispensable for motor neuron differentiation.

Hum Mol Genet. 2016 May 01;25(9):1814-23

Authors: Intoh A, Suzuki N, Koszka K, Eggan K

Abstract
Riboflavin, also known as vitamin B2, is essential for cellular reduction-oxidation reactions, but is not readily synthesized by mammalian cells. It has been proposed that riboflavin absorption occurs through solute carrier family 52 members (SLC52) A1, A2 and A3. These transporters are also candidate genes for the childhood onset-neural degenerative syndrome Brown-Vialetto-Van Laere (BVVL). Although riboflavin is an essential nutrient, why mutations in its transporters result in a neural cell-specific disorder remains unclear. Here, we provide evidence that Slc52a3 is the mouse ortholog of SLC52A3 and show that Slc52a3 deficiency results in early embryonic lethality. Loss of mutant embryos was associated with both defects in placental formation and increased rates of apoptosis in embryonic cells. In contrast, Slc52a3 -/- embryonic stem cell lines could be readily established and differentiated into motor neurons, suggesting that this transporter is dispensable for neural differentiation and short-term maintenance. Consistent with this finding, examination of Slc52a3 gene products in adult tissues revealed expression in the testis and intestine but little or none in the brain and spinal cord. Our results suggest that BVVL patients with SCL52A3 mutations may be good candidates for riboflavin replacement therapy and suggests that either the mutations these individuals carry are hypomorphic, or that in these cases alternative transporters act during human embryogenesis to allow full-term development.

PMID: 26976849 [PubMed - indexed for MEDLINE]

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Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration.

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Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration.

BMC Neurosci. 2017 Aug 16;18(1):64

Authors: Wakasaki T, Niiro H, Jabbarzadeh-Tabrizi S, Ohashi M, Kimitsuki T, Nakagawa T, Komune S, Akashi K

Abstract
BACKGROUND: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells.
RESULTS: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p = 0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced.
CONCLUSIONS: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.

PMID: 28814279 [PubMed - in process]

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Superior petrosal sinus causing superior canal dehiscence syndrome.

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Superior petrosal sinus causing superior canal dehiscence syndrome.

J Laryngol Otol. 2017 Jul;131(7):593-597

Authors: Schneiders SMD, Rainsbury JW, Hensen EF, Irving RM

Abstract
OBJECTIVE: To determine signs and symptoms for superior canal dehiscence syndrome caused by the superior petrosal sinus.
METHODS: A review of the English-language literature on PubMed and Embase databases was conducted, in addition to a multi-centre case series report.
RESULTS: The most common symptoms of 17 patients with superior petrosal sinus related superior canal dehiscence syndrome were: hearing loss (53 per cent), aural fullness (47 per cent), pulsatile tinnitus (41 per cent) and pressure-induced vertigo (41 per cent). The diagnosis was made by demonstration of the characteristic bony groove of the superior petrosal sinus and the 'cookie bite' out of the superior semicircular canal on computed tomography imaging.
CONCLUSION: Pulsatile tinnitus, hearing loss, aural fullness and pressure-induced vertigo are the most common symptoms in superior petrosal sinus related superior canal dehiscence syndrome. Compared to superior canal dehiscence syndrome caused by the more common apical location of the dehiscence, pulsatile tinnitus and exercise-induced vertigo are more frequent, while sound-induced vertigo and autophony are less frequent. There is, however, considerable overlap between the two subtypes. The distinction cannot as yet be made on clinical signs and symptoms alone, and requires careful analysis of computed tomography imaging.

PMID: 28502274 [PubMed - indexed for MEDLINE]

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Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration.

Related Articles

Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration.

BMC Neurosci. 2017 Aug 16;18(1):64

Authors: Wakasaki T, Niiro H, Jabbarzadeh-Tabrizi S, Ohashi M, Kimitsuki T, Nakagawa T, Komune S, Akashi K

Abstract
BACKGROUND: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells.
RESULTS: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p = 0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced.
CONCLUSIONS: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.

PMID: 28814279 [PubMed - in process]

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Superior petrosal sinus causing superior canal dehiscence syndrome.

Related Articles

Superior petrosal sinus causing superior canal dehiscence syndrome.

J Laryngol Otol. 2017 Jul;131(7):593-597

Authors: Schneiders SMD, Rainsbury JW, Hensen EF, Irving RM

Abstract
OBJECTIVE: To determine signs and symptoms for superior canal dehiscence syndrome caused by the superior petrosal sinus.
METHODS: A review of the English-language literature on PubMed and Embase databases was conducted, in addition to a multi-centre case series report.
RESULTS: The most common symptoms of 17 patients with superior petrosal sinus related superior canal dehiscence syndrome were: hearing loss (53 per cent), aural fullness (47 per cent), pulsatile tinnitus (41 per cent) and pressure-induced vertigo (41 per cent). The diagnosis was made by demonstration of the characteristic bony groove of the superior petrosal sinus and the 'cookie bite' out of the superior semicircular canal on computed tomography imaging.
CONCLUSION: Pulsatile tinnitus, hearing loss, aural fullness and pressure-induced vertigo are the most common symptoms in superior petrosal sinus related superior canal dehiscence syndrome. Compared to superior canal dehiscence syndrome caused by the more common apical location of the dehiscence, pulsatile tinnitus and exercise-induced vertigo are more frequent, while sound-induced vertigo and autophony are less frequent. There is, however, considerable overlap between the two subtypes. The distinction cannot as yet be made on clinical signs and symptoms alone, and requires careful analysis of computed tomography imaging.

PMID: 28502274 [PubMed - indexed for MEDLINE]

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Beyond Sentences: Using the Expression, Reception, and Recall of Narratives Instrument to Assess Communication in School-Aged Children With Autism Spectrum Disorder

Purpose

Impairments in the social use of language are universal in autism spectrum disorder (ASD), but few standardized measures evaluate communication skills above the level of individual words or sentences. This study evaluated the Expression, Reception, and Recall of Narrative Instrument (ERRNI; Bishop, 2004) to determine its contribution to assessing language and communicative impairment beyond the sentence level in children with ASD.

Method

A battery of assessments, including measures of cognition, language, pragmatics, severity of autism symptoms, and adaptive functioning, was administered to 74 8- to 9-year-old intellectually able children with ASD.

Results

Average performance on the ERRNI was significantly poorer than on the Clinical Evaluation of Language Fundamentals–Fourth Edition (CELF-4). In addition, ERRNI scores reflecting the number and quality of relevant story components included in the participants' narratives were significantly positively related to scores on measures of nonverbal cognitive skill, language, and everyday adaptive communication, and significantly negatively correlated with the severity of affective autism symptoms.

Conclusion

Results suggest that the ERRNI reveals discourse impairments that may not be identified by measures that focus on individual words and sentences. Overall, the ERRNI provides a useful measure of communicative skill beyond the sentence level in school-aged children with ASD.

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