Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome.
OBJECTIVE
To identify the mutation leading to syndromic choroideremia (CHM) in two families and to define fundus autofluorescence (FAF) in CHM carriers.


METHODS
The ophthalmic and clinical phenotype was investigated including FAF, neuropediatric, otorhinolaryngologic, cardiologic, and nephrologic examinations of three male patients (age, 11-46 years) and three female carriers (age, 11-46 years) from two families. Genomic DNA amplification (PCR) of the REP1 gene as well as adjacent loci was used to determine the molecular basis of the phenotype.


RESULTS
Analysis of genomic DNA revealed large deletions that asymmetrically flank REP1 in both families, ranging from a minimum size of 6.3 and 8.5 mega base pairs (Mbp) to a maximum size of 9.7 and 14.1 Mbp, respectively. In addition to CHM, patients from these families exhibited mild syndromic features, including mental and motor retardation and low-frequency hearing loss. FAF showed a distinctive pattern characterized by small areas of reduced and increased autofluorescence in all female carriers.


CONCLUSIONS
Both CHM families are the first to be described with large deletions that manifest with a mild syndromic phenotype. The location of the deletions indicates that they may allow sublocalization of the syndromic features to the most proximal region of X-linked distal spinal muscular atrophy (DSMAX) and Martin-Probst deafness mental retardation syndrome (MPDMRS). The FAF pattern is specific to CHM carriers and thus will help to identify and differentiate between carriers of other X-linked recessive carrier states such as in X-linked retinitis pigmentosa.
Poloschek
Charlotte M
CM
Department of Ophthalmology, University of Freiburg, Freiburg, Germany. charlotte.poloschek@uniklinik-freiburg.de
Kloeckener-Gruissem
Barbara
B
Hansen
Lutz L
LL
Bach
Michael
M
Berger
Wolfgang
W
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015794:Choroideremia / Q000235:genetics*; D041321:Chromosomes, Human, X; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D003638:Deafness / Q000235:genetics*; D005190:Family; D005260:Female; D006580:Genetic Carrier Screening; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics; D017384:Sequence Deletion; D013577:Syndrome
D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D017931:DNA Primers; D004247:DNA