Identification of a novel mutation in the CHD7 gene in a patient with CHARGE syndrome
A 21 day-old girl was transferred to Samsung Medical Center due to extubation failure. The baby was born at the 35+1 weeks of gestation by emergency cesarean section due to spontaneous rupture of the membranes and premature labor. Apgar scores were 2 at 1 minute and 8 at 5 minutes. When the baby was born, she did not cry and became cyanotic and lethargic. Positive pressure ventilation was not effective, so endotracheal intubation was performed in the delivery room. At birth, weight, length, and head circumference were 2,030 g (25th percentile), 49 cm (75th-90th percentile), and 35 cm (>90th percentile), and she had low set ears. A large patent ductus arteriosus (PDA) was found and ligated 12 days after birth.\nWe conducted osteomeatal unit computed tomography (CT) to find the cause of extubation failure. CT scan showed bilateral choanal atresia, atresia of the left external auditory canal, and stenosis of the right auditory canal (). Thirty-five days after birth, she underwent a repair operation of the choanae, and we tried to extubate again. However, she was reintubated with an endotracheal tube because of sustained desaturation and tachypnea. We considered that the cause of extubation failure was an upper airway problem. She was identified to have postglottic stenosis through laryngomicrosurgery (). Forty-two days after birth, a tracheostomy was performed, and respiration stabilized without respiratory support.\nThe patient had a left aortic arch with aberrant origin of the right subclavian artery on chest CT and minimal left pulmonary artery hypoplasia without focal stenosis on echocardiography. Based on these results, we conducted the ophthalmic examination to identify other features of CHARGE syndrome, and found coloboma in her both eyes. Because she met two out of the three major criteria and two of the five minor diagnostic criteria, we concluded that she had typical CHARGE syndrome.\nWritten informed consent was obtained for a molecular genetic analysis of the CHD7 gene mutation from the parents. Direct sequencing analysis of the CHD7 gene was performed with genomic DNA isolated from peripheral blood leukocytes. As a result, a c.3896T>C (p. leu1299Pro) missense mutation in exon 16 of the CHD7 gene was detected, which has not been reported previously (). A familial study revealed that neither of the parents had the mutation. The polymorphism phenotyping program and the sorting intolerant from tolerant program predicted "possibly damaging" and "not tolerated." The amino acid residue L1299 is highly conserved across different species, and the L1299P variation does not occur in 200 control chromosomes from 100 healthy individuals.\nAfter discharge at 2 months of age, she has been followed up at the outpatient clinic regularly. At present, she is 11 months old and is using a hearing aid because of sensorineural hearing loss. Since she has had recurrent aspiration; thus G-tube feeding is required. Her height was 10th-25th percentile, body weight was 5th-10th percentile, and head circumference was 10th-25th percentile. The patient can sit alone but cannot stand with support. Hypoplasia of both kidneys was identified by abdominal ultrasonography, which was performed at 5 months of age. She has met two of the three major criteria and four of the five minor diagnostic criteria for CHARGE syndrome.