A novel 11p13 microdeletion encompassing PAX6 in a Chinese Han family with aniridia, ptosis and mental retardation.

Ping Hu,Ping Hu,Yan Wang,Yan Wang,Jing Zhou,Jing Zhou,Lulu Meng,Long Yi,Lulu Meng,Fengchang Qiao,Zhengfeng Xu,Zhengfeng Xu,Dingyuan Ma

doi:10.1186/s13039-015-0110-2

Abstract

PurposeTo explore possible genetic aberrations in a Chinese family with aniridia, ptosis and mental retardation, and provide genetic evidence for the prenatal diagnosis.Methods14 exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Multiplex ligation-dependent probe amplification (MLPA) technique was employed to further explore gene alterations of PAX6. Single nucleotide polymorphisms-array (SNP-array) assay was applied to screen potential pathologic genome-wide copy number variations (CNV).ResultsThere were no detectable pathogenic mutations in the 14 exons of PAX6 in the proband. MLPA indicated a heterozygous deletion encompassing all PAX6 gene regions covered and a partial upstream region. SNP-array assay detected a heterozygous 11p13 microdeletion with a length of 518 kb in the proband, spanning two whole annotated genes, elongation factor protein 4 (ELP4), the paired box gene 6 (PAX6), and partial IMP1 inner-mitochondrial membrane (IMMP1L) gene. SNP-array revealed her affected brother carried the identical deletion.ConclusionsThe 518 kb heterozygous deletion in 11p13 encompassing PAX6 should be the genetic etiology for the familial aniridia.

Highlights

Congenital aniridia (OMIM 106210) is a kind of eye disorder characterized by complete or partial hypoplasia of the iris
We report on a novel genomic microdeletion including paired box gene 6 (PAX6) in a small Chinese family with aniridia, cataract, ptosis and mental retardation detected by SNParray assay
Multiplex ligation-dependent probe amplification (MLPA) results revealed that the height of all these probes in the elongation factor protein 4 (ELP4) and PAX6 displayed nearly half-dose reduced, whereas probes targeting genes up- or downstream to the deletion such as DCDC1, RCN1,WT1, exhibited nearly the same height as the normal

Summary

Introduction

Congenital aniridia (OMIM 106210) is a kind of eye disorder characterized by complete or partial hypoplasia of the iris. About two-thirds of reported aniridia cases were familial and showed a dominant inheritance manner with nearly complete penetrance, the remaining one-third were sporadic [2]. PAX6 (OMIM 607108), a well-known aniridia disease-causing gene located in chromosome 11p13 region, contains 14 exons and encodes a protein of 422 amino acids. Previous studies demonstrated that people harboring PAX6 mutation displayed a clinical symptom spectrum including aniridia, corneal opacification, keratitis, cataract, glaucoma, lens dislocation, ciliary body hypoplasia, foveal hypoplasia, strabismus, nystagmus, Peter’s anomaly, optic nerve defects [5], hyposmia, abnormal inter-hemispheric auditory transfer [6], impaired islet function [7] and brain structure abnormalities [8]. Approximately 357 intragenic mutations have been documented in the PAX6 mutation database (http://www.hgu.mrc.ac.uk/Softdata/ PAX6/), while microdeletion cases associated with PAX6 region were rare

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