X-linked Opitz G/BBB syndrome: identification of a novel mutation and prenatal diagnosis in a Korean family

Abstract

X-linked Opitz G/BBB syndrome (XLOS; MIM 300000) is a rare multiple congenital anomaly disorder that is characterized by facial anomalies, laryngeal/tracheal/esophageal defects and genitourinary abnormalities. XLOS is caused by mutations in the MID1 gene which encodes a microtubule-associated RING-Bbox-Coiled-coil (RBCC) protein. We recently found a four-year Korean male patient who was suspected of having XLOS. Mutation analysis of the MID1 gene in the patient and his mother demonstrated that the patient had a novel insertion mutation (c.1798_1799-insC), and his mother was a heterozygous carrier of the mutation. After identification of the causative mutation in this family, prenatal diagnosis of two consecutive fetuses were successfully undertaken. This is the first report on a genetically confirmed case of XLOS in Korea.

Fig. 1

Pedigree and sequence of proband and proband's mother with a MID1 mutation. (A) Pedigree of family in present study. Squares and circles represent males and females, respectively. Blackened symbols indicate individuals with X-linked Opitz syndrome confirmed by MID1 mutation analysis. Small black dots within the circle indicate carrier state confirmed by MID1 mutation analysis. (B) Direct sequencing of the MID1 gene shows overlapping peaks from the nucleotide c.1798A (arrow) in the proband's mother due to a heterozygous 1 bp insertion of cytosine (c.1798_1799insC; p.His600ProfsX12). The proband was hemizygous for the mutation.