A novel mutation (296 del G) of the SOX9 gene in a patient with campomelic syndrome and sex reversal

Abstract

The human SOX9 gene is responsible for the campomelic syndrome (CMPS) and sex reversal. This gene encodes a transcription factor containing a DNA binding domain homologous to the SRY high mobility group (HMG) domain. A novel mutation of SOX9, i.e. a single G deletion in one allele at nt 296 from A of the first ATG in the open reading frame, was identified in a patient with CMPS with sex reversal. The deletion resulted in a frameshift mutation upstream of the HMG box and a stop codon 30 bp downstream of the HMG box. The predicted truncated SOX9 protein contained 108 amino acids instead of the 509 amino acids of the normal SOX9 protein, removing nearly 80% of the SOX9 protein, including the HMG and the C-terminal transactivation domain. Most patients with CMPS reported previously died within the neonatal period. Our findings that the patient has survived, although has been in daily need of mechanical ventilation support for 5 years and 3 months despite a severely impaired SOX9 protein, do not support a linear relationship between the type of mutation and severity of the clinical outcome.

The Battle of the Sexes: Human Sex Development and Its Disorders

“…DSD and SOX9 regulatory elements Several point mutations and small insertions have been identified in patients with CD and 46,XY DSD (Cameron et al 1996;Foster et al 1994;Ninomiya et al 2000;Pop et al 2005;Wagner et al 1994). …”

A novel SOX9 mutation, 972delC, causes 46,XY sex-reversed campomelic dysplasia with nephrocalcinosis, urolithiasis, and dysgerminoma

“…Genomic DNA was extracted from whole blood using a standard method. Amplification of the coding sequence of SOX9 by polymerase chain reaction (PCR) was carried out using 6 overlapping primer pairs as has been described previously [3,4]. Cycle sequencing of each segment was carried out in the forward and reverse directions.…”

A rare case of lethal campomelic dysplasia

“…In addition, a group of respiratory anomalies that includes lungs and chest of a small size, narrow air-passages, tracheomalacia, laryngomalacia associated with cleft palate, micrognathia, and hypotonia may be present. 11 The skeletal features that were the most prominent characteristics of CD as presented in our case including hypoplastic scapula, bilateral bowing of femurs, a small thoracic cavity and kyphoscoliosis.…”