Isolated colobomatous microphthalmia 7 (MCOPCB7) is an ocular disorder characterized by small eyes and coloboma formation. Coloboma arises from defective fusion of the embryonic optic fissure causing defective tissue formation in certain ocular structures including the iris, choroid, and retina.
Colobomatous microphthlamia is genetically heterogeneous and may be isolated or featured in multiple syndromic disorders. MCOPCB7 is a non-syndromic disorder caused by ABCB6 deficiency.
MCOPCB7 is an autosomal dominant disorder caused by heterozygous loss-of-function missense mutations in the ABCB6 gene; this was identified through exome sequencing of patients lacking variants in known MCOPCB genes.
ABCB6 belongs to the Multi-Drug Resistance and Transporter associated Antigen Processing (MDR/TAP) subgroup of the ABC superfamily. The gene encodes a transmembrane protein located on mitochondrial and plasma membranes; its function includes heme biosynthesis, heme binding and transport, cellular iron ion homeostasis, porphyrin import and export, antigen presentation, and involvement in brain development. ABCB6 exhibits ubiquitous tissue expression including high retinal protein expression; it is hypothesized that ABCB6 is involved in eye development through transport of signaling molecules and metal homeostasis.
Al-Shamsi et al., 2016 performed Whole Exome Sequencing in 85 Emirati patients who were admitted to the metabolic unit with un-diagnosable inborn errors of metabolism and other genetic disorders. Among the cohort in whom variants of uncertain significance were likely pathogenic, 1 patient harboring a mutation in ABCB6 and CHD7 was diagnosed with isolated microphthalmia with coloboma 7 (MCOPCB7). The patient had presented with microphthlamia, autism, and involuntary hand movement; the patient’s father also presented with microphthalmia and exhibited identical mutations.
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