Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure.

Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate regulator of thyroid and lung morphogenesis and function in humans. We report 2 female siblings with congenital thyroid dysfunction and recurrent acute respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3, resulting in haploinsufficiency for the NKX2.1 gene. This observation further supports a physiologic role for thyroid transcription factor-1 in early human thyroid and pulmonary function.