Kenna Margaret A, Feldman Henry A, Neault Marilyn W, Frangulov Anna, Wu Bai-Lin, Fligor Brian, Rehm Heidi L
Department of Otolaryngology and Communication Enhancement, Children's Hospital Boston, 300 Longwood Ave, LO-367, Boston, MA 02115, USA.
Arch Otolaryngol Head Neck Surg. 2010 Jan;136(1):81-7. doi: 10.1001/archoto.2009.202.
To document the audiologic phenotype of children with biallelic GJB2 (connexin 26) mutations, and to correlate it with the genotype.
Prospective, observational study.
Tertiary care children's hospital.
Infants and children with sensorineural hearing loss (SNHL).
Sequencing of the GJB2 (connexin 26) gene.
Degree and progression of SNHL.
From December 1, 1998, through November 30, 2006, 126 children with biallelic GJB2 mutations were identified. Of the 30 different mutations identified, 13 (43%) were truncating and 17 (57%) were nontruncating; 62 patients had 2 truncating, 30 had 1 truncating and 1 nontruncating, and 17 had 2 nontruncating mutations. Eighty-four patients (67%) initially had measurable hearing in the mild to severe range in at least 1 of 4 frequencies (500, 1000, 2000, or 4000 Hz). Of these 84 patients with residual hearing, 47 (56%) had some degree of progressive hearing loss. Patients with 2 truncating mutations had significantly worse hearing compared with all other groups. Patients who had 1 or 2 copies of either an M34T or a V37I allele had the mildest hearing loss.
Hearing loss owing to GJB2 mutations ranges from mild to profound and is usually congenital. More than 50% of patients will experience some hearing loss progression, generally gradually but occasionally precipitously. Hearing loss severity may be influenced by genetic factors, such as the degree of preserved protein function in nontruncating mutations, whereas hearing loss progression may be dependent on factors other than the connexin 26 protein. Genetic counseling for patients with GJB2 mutations should include the variable audiologic phenotype and the possibility of progression.
记录双等位基因GJB2（连接蛋白26）突变儿童的听力学表型，并将其与基因型相关联。
前瞻性观察性研究。
三级护理儿童医院。
感音神经性听力损失（SNHL）的婴儿和儿童。
对GJB2（连接蛋白26）基因进行测序。
SNHL的程度和进展情况。
从1998年12月1日至2006年11月30日，共鉴定出126例双等位基因GJB2突变儿童。在鉴定出的30种不同突变中，13种（43%）为截短突变，17种（57%）为非截短突变；62例患者有2种截短突变，30例有1种截短突变和1种非截短突变，17例有2种非截短突变。84例患者（67%）最初在4个频率（500、1000、2000或4000Hz）中的至少1个频率上有轻度至重度范围内的可测量听力。在这84例有残余听力的患者中，47例（56%）有一定程度的听力损失进展。与所有其他组相比，有2种截短突变的患者听力明显更差。有M34T或V37I等位基因1个或2个拷贝的患者听力损失最轻微。
由GJB2突变引起的听力损失范围从轻度到重度，通常为先天性。超过50%的患者会出现一定程度的听力损失进展，一般为逐渐进展，但偶尔也会急剧进展。听力损失的严重程度可能受遗传因素影响，如非截短突变中保留的蛋白质功能程度，而听力损失的进展可能取决于连接蛋白26蛋白以外的因素。对GJB2突变患者进行遗传咨询时应包括可变的听力学表型和进展的可能性。
