RESUMEN

Non-syndromic hearing loss (NSHL) is a common neurosensory disease with an extreme genetic heterogeneity which has been linked to variants in over 120 genes. The LOXHD1 gene (DFNB77), encoding lipoxygenase homology domain 1, is a rare hearing loss gene found in several populations. To evaluate the importance of LOXHD1 variants in Chinese patients with NSHL, we performed genetic analysis on LOXHD1 in 2,901 sporadic Chinese patients to identify the aspect and frequency of LOXHD1 causative variants. Next-generation sequencing using a custom gene panel of HL was conducted on 2,641 unrelated patients and whole-exome sequencing on the remaining 260 patients. A total of 33 likely causative variants were identified in 21 patients, including 20 novel variants and 13 previously reported pathogenic variants. Each of the 20 novel variants was evaluated according to ACMG criteria. These findings showed that causative variants in LOXHD1 were found in about 0.72% (21/2,901) of Chinese NSHL patients. This study is by far the largest number of novel variants identified in this gene expanding the range of pathogenic variants in LOXHD1, and suggests that variants in this gene occur relatively commonly in Chinese NSHL patients. This extensive investigation of LOXHD1 in Chinese NSHL patients proposed six recurrent LOXHD1 variants. These findings may assist in both molecular diagnosis and genetic counseling.

RESUMEN

Hereditary hearing loss is characterized by remarkable phenotypic heterogeneity. Patients with the same pathogenic mutations may exhibit various hearing loss phenotypes. In the Chinese population, the c.235delC mutation is the most common pathogenic mutation of GJB2 and is closely related to hereditary recessive hearing loss. Here, we investigated the hearing phenotypes of patients with hearing loss associated with the homozygous c.235delC mutation, paying special attention to asymmetric interaural hearing loss. A total of 244 patients with the GJB2 c.235delC homozygous mutation encountered from 2007 to 2015 were enrolled. The severity of hearing loss was scaled with the American Speech-Language-Hearing Association (ASHA). Auditory phenotypes were analyzed, and three types of interaural asymmetry were defined based on audiograms: Type A (asymmetry of hearing loss severity), Type B (asymmetry of audiogram shape), and Type C (Type A plus Type B). Of the 488 ears (244 cases) examined, 71.93% (351) presented with profound hearing loss, 14.34% (70) with severe hearing loss, and 9.43% (46) with moderate to severe hearing loss. The most common audiogram shapes were descending (31.15%) and flat (24.18%). A total of 156 (63.93%) of the 244 patients exhibited asymmetric interaural hearing loss in terms of severity and/or audiogram shape. Type A was evident in 14 of these cases, Type B in 106, and Type C in 36. In addition, 211 of 312 ears (67.63%) in the interaural hearing asymmetry group showed profound hearing loss, and 59 (18.91%) exhibited severe hearing loss, with the most common audiogram shapes being flat (27.88%) and descending (22.12%). By contrast, in the interaural hearing symmetry group, profound hearing loss was observed in 140 ears (79.55%), and the most common audiograms were descending (46.59%) and residual (21.59%). Hearing loss associated with the GJB2 c.235delC homozygous mutation shows diverse phenotypes, and a considerable proportion of patients show bilateral hearing loss asymmetry.

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RESUMEN

BACKGROUND: It is of high incidence of brain injuries in premature infants, so it is necessary to diagnose and treat the brain injury early for neonatal clinical practice. We are aimed to investigate the relationship between early postnatal cranial ultrasonography and psychomotor and mental development in prematrue infants at the age of 12 months. METHODS: Two-hundred and eight premature infants were selected and underwent follow-up from January, 2007 to November, 2012. Cranial ultrasonography was performed on them. The developmental outcomes of these premature infants at the age of 12 months were assessed by the psychomotor developmental index (PDI) scale and mental development index (MDI). The relationship between ultrasonic gray-scale value and PDI and MDI was analyzed. RESULTS: The worse prognosis for psychomotor and mental development was associated with the gestational age, Apgar score(1 min), gender, chorioamnionitis, duration of mechanical ventilation and duration of mechanic ventilation. The differences between the prognosis of psychomotor and mental development, and peri-intraventricular hemorrhage (PIVH) and periventricular white matter damage (PWMD), were statistically significant (P<0.05). There were also significant differences between the early postnatal ultrasonic gray-scale value and prognoses of both psychomotor development and mental development (P<0.05). There were negative correlations between ultrasonic gray-scale and both PDI and MDI (r=-0.753, P<0.05; r=-0.764, P<0.05). CONCLUSIONS: The early postnatal cranial ultrasonography can assist to predict the prognosis of psychomotor and mental development for premature infants. The higher grade of PIVH and PWMD was associated with the worse prognosis of psychomotor and mental development.

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