Maternal isodisomy for chromosome 2p causing severe congenital hypothyroidism

Severe congenital hypothyroidism (CH) due to a total iodide organification defect (TIOD) is usually due to mutations in the thyroid peroxidase (TPO) g ene located at chromosome 2p25. A homozygous deletion [Delta T2512 (codon 8 08)] in exon 14 was identified in a patient with classical TIOD. The transm ission 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 demon strated 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 h omologs. A normal karyotype was found in the propositus, his parents and si ster. We conclude that the homozygosity in the patient is due to partial ma ternal 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 pa rtial maternal isodisomy for chromosome 2p (2pter - 2p12) is compatible wit h a minimal influence on normal development.