Bakker B, Bikker H, Hennekam R C, Lommen E J, Schipper M G, Vulsma T, de Vijlder J J
Academic Medical Center, University of Amsterdam, Emma Children's Hospital AMC, Division of Pediatric Endocrinology, 1100 DE Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 2001 Mar;86(3):1164-8. doi: 10.1210/jcem.86.3.7313.
Severe congenital hypothyroidism (CH) due to a total iodide organification defect (TIOD) is usually due to mutations in the thyroid peroxidase (TPO) gene located at chromosome 2p25. A homozygous deletion [DeltaT2512 (codon 808)] in exon 14 was identified in a patient with classical TIOD. The transmission pattern of the TPO gene in this family was anomalous; the mother was heterozygous for the deletion; and the mutation was absent in the father. Polymorphic short tandem repeat (STR) markers confirmed paternity and demonstrated on chromosome 2 that the propositus was homozygous for most markers on chromosome 2p and that these were identical to one of the maternal 2p homologs. A normal karyotype was found in the propositus, his parents and sister. We conclude that the homozygosity in the patient is due to partial maternal isodisomy of the short arm of chromosome 2, carrying a defective TPO gene. The patient, born small for gestational age, develops and grows well and appears healthy (while being treated with thyroxine) and has a normal phenotype except for a unilateral preauricular skin tag. This shows that partial maternal isodisomy for chromosome 2p (2pter - 2p12) is compatible with a minimal influence on normal development.
由于全碘有机化缺陷（TIOD）导致的严重先天性甲状腺功能减退症（CH）通常是由位于2号染色体2p25的甲状腺过氧化物酶（TPO）基因突变引起的。在一名典型TIOD患者中发现了外显子14中的纯合缺失[DeltaT2512（密码子808）]。该家族中TPO基因的遗传模式异常；母亲为该缺失的杂合子；父亲不存在该突变。多态性短串联重复序列（STR）标记证实了亲子关系，并在2号染色体上表明，先证者在2号染色体短臂上的大多数标记是纯合的，且这些标记与母亲的一条2号染色体短臂同源。先证者及其父母和妹妹的核型均正常。我们得出结论，患者的纯合性是由于携带缺陷TPO基因的2号染色体短臂的部分母源性等二体性。该患者出生时孕周小，发育和生长良好，（接受甲状腺素治疗时）看起来健康，除了有一个单侧耳前皮肤赘生物外，具有正常的表型。这表明2号染色体短臂（2pter - 2p12）的部分母源性等二体性与对正常发育的最小影响是相容的。
