Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

Abstract

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa

“…Bae et al 22 suggested that molecular genetic diagnosis would be helpful for proper diagnosis of choroidemia. In the present study, 5 (5.3%) of 94 subjects initially diagnosed with RP were shown to have CHM mutation by WES.…”

The genetic counseling in a patient affected by choroideremia solved with the whole-exome sequencing approach

“…The differential diagnosis for choroideremia includes other inherited retinal disorders such as gyrate atrophy and retinitis pigmentosa. [ 8 9 ] WES may be useful when a genetic syndrome is suspected during pre-conception counseling. Genetic counseling may be given once exome sequencing and clinical findings support a hereditary disorder.…”

Coroideremia familiar: reporte de caso con énfasis en la evolución clínica y adquisición de discapacidad visual

“…Algunos autores han demostrado que en la coroideremia se evidencia la reducción de la acidificación lisosómica y retrasos en la degradación de fagosomas de las células del EPR. Lo anterior desencadena una acumulación de material similar a la lipofuscina, aspecto que provoca la degeneración de las células del EPR y como consecuencia, pérdida progresiva de la Agudeza Visual (AV) hasta ceguera 19 .…”

“…Las mutaciones del gen CHM pueden dar como resultado una deleción completa o un producto génico no funcional, causando truncamiento, perdida de dominio funcional o ausencia de la proteína 6,9,19,21 . Hasta el 15% de las mutaciones en el gen CHM son deleciones totales o parciales, donde incluso las deleciones de genes contiguos en el cromosoma X, que incluyen la supresión de Xq21, puedan causar casos de coroideremia.…”