Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings

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• 作者：Malte Spielmann^a ; ^b ; Gabriele Reichelt^c ; Christoph Hertzberg^c ; Marc Trimborn^a ; Stefan Mundlos^a ; ^b ; Denise Horn^a ; Eva Klopocki^a ; ^b ; ^{eva.klopocki@charite.de"" rel=""nofollow}
• 关键词：Homozygous deletion 15q13.3 ; Mental retardation ; Array CGH ; Macrocytosis ; Retinal dysfunction ; KLF13 ; TRPM1
• 刊名：European Journal of Medical Genetics
• 出版年：2011
• 出版时间：July-August 2011
• 年：2011
• 卷：54
• 期：4
• 页码：e441-e445
• 全文大小：606 K

文摘

The heterozygous 15q13.3 microdeletion syndrome (MIM #612001) was first described by Sharp et al. in 2008. So far four patients with 15q13.3 homozygous or compound heterozygous microdeletions have been identified. Here we report a non-consanguineous family with two affected siblings carrying a homozygous microdeletion of 1.5 Mb at the 15q13.3 locus. They presented with congenital retinal dysfunction, refractory epilepsy, encephalopathy, mental retardation, repetitive hand movements, severe muscular hypotonia and macrocytosis. Dysmorphic facial features are synophrys and bilateral proptosis. The siblings carry a homozygous microdeletion at 15q13.3 of 1.5 Mb including the genes ARHGAP11B, MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, and CHRNA7. The absence of CHRNA7 has been suggested as a cause of refractory seizures. According to knock-out experiments the deletion of KLF13 could be an explanation for macrocytosis. The homozygous loss of TRPM1 could be a possible explanation for congenital retinal dysfunction.