Interstitial deletion in 3q in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and microcephaly, mild mental retardation and growth delay: clinical report and review of the literature.
We present a boy with blepharophimosis, ptosis, epicanthus inversus, microcephaly, mild mental retardation, and growth delay. Chromosomal analysis revealed a male karyotype with an interstitial deletion in the long arm of chromosome 3. DNA-analysis showed that the deletion is of maternal origin and encompasses the region between markers D3S1535 and D3S1593. The deletion contains not only the FOXL2 gene, but also the gene encoding ataxia-telangiectasia and Rad3-related protein (ATR). Mutations in FOXL2 have been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). ATR has been identified as a candidate gene for Seckel syndrome, an autosomal recessive syndrome that comprises growth retardation, microcephaly, and mental retardation. We hypothesize that our patient has a contiguous gene syndrome and that the non-BPES-associated abnormalities (microcephaly, mild mental retardation, and growth delay) are the result of the deletion of the maternal ATR gene. However, it has not yet been excluded that haploinsufficiency of some other gene in this region plays a role.
de Ru
M H
MH
Department of Clinical Genetics and Human Genetics, V.U. University Medical Center, Amsterdam, The Netherlands.
Gille
J J P
JJ
Nieuwint
A W M
AW
Bijlsma
J B
JB
van der Blij
J F
JF
van Hagen
J M
JM
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins; D016569:Blepharophimosis / Q000473:pathology; D001763:Blepharoptosis / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005143:Eyelids / Q000002:abnormalities; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D017353:Gene Deletion; D006130:Growth Disorders / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000473:pathology*; D007621:Karyotyping; D008831:Microcephaly / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases