RESUMEN
Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.
Asunto(s)
Sordera , Factores de Transcripción Forkhead , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Canales de Potasio de Rectificación Interna , Transportadores de Sulfato , Femenino , Humanos , Masculino , Alelos , Sordera/genética , Variaciones en el Número de Copia de ADN , Factores de Transcripción Forkhead/genética , Genotipo , Pérdida Auditiva/genética , Pérdida Auditiva Sensorineural/genética , Mutación , Fenotipo , Transportadores de Sulfato/genética , Acueducto Vestibular , Recién Nacido , Canales de Potasio de Rectificación Interna/genéticaRESUMEN
BACKGROUND: To provide the anatomic basis for the clinical application of the transpedicular screw fixation. MATERIALS AND METHODS: Thirty spine (C2-L5) specimens were used. The width of the pedicle cortex and width of the pedicle medullary cavity (WPC and WPMC), and the height of the pedicle cortex and height of the pedicle medullary cavity (HPC and HPMC) were measured at the isthmus of the pedicle using computed tomography (CT) scanning. RESULTS: Width of the pedicle medullary cavity changed in a three-dovetailed-saddle shape with four peaks and three valleys, namely C2 (high), C4`5 (low), T2 (high), T4 (the lowest), T12 (high), L1 (low) and L5 (the highest). HPMC of the cervical pedicle changed in a saddle shape, gradually increasing from C5-L5. WPC, WPMC, HPC and HPMC showed a regular change, respectively. In each segment, the superior border of the pedicle cortex had a nearly consistent thickness to the interior border within an identical pedicle, while the pedicle cortex thickness radio of the medial and lateral border was nearly 3:1 among the cervical pedicles, 2:1 among thoracic pedicles, and 1:1 among lumbar pedicles. CONCLUSIONS: Both HPMC and WPMC are the dominant factors for the choice of screw diameter, but HPMC should also be considered in C2-T1 pedicles, especially C6 and C7. Additionally, the screw for C3-6 or T4-6 pedicles should be about 3.0 mm in diameter.