Gonzalez Trevino O, Karamanoglu Arseven O, Ceballos C J, Vives V I, Ramirez R C, Gomez V V, Medeiros-Neto G, Kopp P
Department of Nuclear Medicine and Thyroid Clinic, Instituto Nacional Nutrition S. Zubiran, Mexico City, Mexico.
Eur J Endocrinol. 2001 Jun;144(6):585-93. doi: 10.1530/eje.0.1440585.
The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney.
To perform a detailed clinical and molecular analysis of patients with Pendred's syndrome from four patients from three unrelated Mexican families.
Thyroid function tests, perchlorate test, thyroid scintigraphy, audiometry, computer tomography and magnetic resonance imaging were performed in all affected individuals. Haplotype analyses were performed using microsatellite markers flanking the PDS locus, and the PDS gene was submitted to direct sequence analysis.
All patients presented with sensorineural deafness, Mondini malformations of the cochlea, an enlarged vestibular aqueduct, goiter, and a positive perchlorate test. Two patients were hypothyroid, two individuals were euthyroid. Sequence analysis revealed a complex homozygous deletion/insertion mutation at the end of exon 4 in the index patient of family 1 resulting in a premature stop codon at position 138. In family 2, the affected individuals were compound heterozygous for a splice acceptor mutation (IVS2 -1G>A) and a 1231G>C transversion substituting alanine 411 by proline (A411P). In family 3, the index patient was found to be homozygous for a transversion 412G>T in exon 4 replacing valine 138 by phenylalanine (V138F).
All patients included in this study presented with the classic Pendred syndrome triad and molecular analysis revealed pendrin mutations as the underlying cause. The identification of three novel mutations, one of them of complex structure, expands the spectrum of mutations in the PDS gene and emphasizes that they display marked allelic heterogeneity.
常染色体隐性遗传性彭德莱德综合征的特征为先天性感音神经性耳聋、甲状腺肿以及碘有机化障碍。它由彭德莱德综合征（PDS）基因突变引起，该基因编码的pendrin是一种氯/碘转运体，在甲状腺、内耳和肾脏中表达。
对来自三个不相关墨西哥家庭的四名患者进行彭德莱德综合征的详细临床和分子分析。
对所有受影响个体进行甲状腺功能测试、高氯酸盐试验、甲状腺闪烁扫描、听力测定、计算机断层扫描和磁共振成像。使用位于PDS基因座侧翼的微卫星标记进行单倍型分析，并对PDS基因进行直接序列分析。
所有患者均出现感音神经性耳聋、耳蜗蒙迪尼畸形、前庭导水管扩大、甲状腺肿以及高氯酸盐试验阳性。两名患者甲状腺功能减退，两名甲状腺功能正常。序列分析显示，家系1的先证者外显子4末端存在复杂的纯合缺失/插入突变，导致第138位出现过早的终止密码子。在家族2中，受影响个体为剪接受体突变（IVS2 -1G>A）和1231G>C颠换的复合杂合子，该颠换使丙氨酸411被脯氨酸取代（A411P）。在家族3中，先证者被发现外显子4中412G>T颠换纯合，使缬氨酸138被苯丙氨酸取代（V138F）。
本研究纳入的所有患者均表现出典型的彭德莱德综合征三联征，分子分析显示pendrin突变是根本原因。三个新突变的鉴定，其中一个结构复杂，扩展了PDS基因突变谱，并强调它们表现出明显的等位基因异质性。
