A.O. Khan, N. Patel, S.S. Alzahrani, S.T. Arold, F.S. Alkuraya
Ophthalmic Genet., 1, pp. 1-7, (2018)
The purpose of this study is to
uncover the genetic cause for non-syndromic macular "coloboma"
(pseudocoloboma) in three brothers from a consanguineous family.
mapping for the three affected brothers and whole-exome sequencing in
one affected brother, followed by confirmatory Sanger sequencing and
segregation analysis of the candidate gene for all immediate family
members; molecular modeling of the candidate mutation; and review of
clinical, imaging, and laboratory findings.
otherwise-healthy brothers (age 10, 10, and 6 years) had macular
pseudocoloboma. Both parents and the fourth brother were not affected.
Parents were first cousins. A novel homozygous missense variant in
claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated
with the phenotype, and molecular modeling predicts an unfavorable
effect to protein function. All prior reported biallelic CLND19
mutations cause symptomatic hypomagnesemia with hypercalciuria and
nephrocalcinosis, often with concurrent macular pseudocoloboma. However,
general physical assessment, metabolic profile, and renal imaging for
the three affected brothers were normal.
homozygous CLDN19 mutation can cause macular pseudocoloboma without
evidence for systemic disease in children. This is the first reported
family with CLDN19 mutations to have an ocular phenotype only; however,
those identified to harbor biallelic CLDN19 mutations should be
considered at risk for the extraocular manifestations that have
previously been associated with mutations in the gene.