CCDD Phenotype Associated with a Small Chromosome 2 Deletion

Abstract

This patient's chromosomal abnormality affected only one gene that currently seems involved only in muscle development. All other genes currently associated with the CCDDs affect neurologic development. Genetic information from this patient implies that genes involved in development and maintenance of extraocular muscles can cause congenital ocular motility disorders as well.

Microdeletions involving Chromosomes 12 and 22 Associated with Syndromic Duane Retraction Syndrome

“…5 Alternatively, RNF34 plays a role in muscle development, and abnormal muscle development has been potentially related to one CCDD in the recent past. 51 PPARA is a transcription factor that might, when mutated, have an effect on ocular motility similar to KIF21A and TUBB3 mutations. 6,7 In addition, PPARA may interact with nearby genes in the 22q11.2 locus, yielding some components of the velo-cardio-facial syndrome.…”

Duane Retraction Syndrome Associated with a Small X Chromosome Deletion

“…There is also a previous report of a congenital ocular motility abnormality with globe retraction similar to DRS associated with the gene XIRP2 involved predominantly in muscle development, implying that the primary genetic abnormality in some patients with congenital ocular motility abnormalities may be related to muscle development. 1 Nevertheless, the presence of DRS in the patient described in this study with a heterozygous dystrophin mutation and in three other patients with DMD raises the possibility that the frequency of DRS may be affected by dystrophin mutations. In DMD, functional dystrophin is also missing in postsynaptic regions of the cerebellum and cerebral cortex, and central nervous system involvement in DMD is confirmed by the presence of cognitive deficits and increased cortical excitability.…”

“…The array CGH assay was performed according to the manufacturer's instructions as detailed elsewhere. 1 Data were analyzed using the Affymetrix Chromosome Analysis Suite, v1.2, software. In the absence of internationally recognized criteria for analysis of high-resolution array CGH results, we devised preliminary criteria for a copy number variant (CNV) to be considered potentially pathologic, including: (1) it was not reported in the Database of Genomic Variants (DGV; http://projects.tcag.ca/variation/) among normal controls; (2) it was not present in 150 healthy controls of similar ethnicity; (3) it included an area of the genome encompassing one or more functional genes; and (4) it segregated with the phenotype and was not present in unaffected family members.…”

Chromosome 6 microdeletion in a patient with syndromic congenital cranial dysinnervation disorder

“…The CCDDs can be monogenic or chromosomal in origin. Although chromosomal copy number variations (CNVs) has been reported in patients with syndromic CCDDs,2 but there are still patients for whom the genetic basis has not been identified yet. In this report, we describe the evaluation of a girl with CCDD and other congenital abnormalities by high-resolution array-comparative genomic hybridization (array CGH), which revealed a microdeletion in chromosome 6.…”

“…The complete coding regions of the SALL4, CHN1, HOXA1, and TUBB3 genes and exons 8, 20, and 21 considered hotspot for mutations in the KIF21A gene were sequenced according to protocols described previously 2. The Affymetrix Cytogenetics Whole-Genome 2.7M array (Affymetrix Inc., Santa Clara, CA, USA) was used to detect chromosomal aberrations across the entire genome as described elsewhere 2. The data analysis was carried out using Affymetrix ® Chromosome Analysis Suite v1.2 (ChAS) Software (Affymetrix Inc. CA, USA).…”