小头畸形
生物
先证者
错义突变
遗传学
自闭症谱系障碍
表型
自闭症
基因
突变
心理学
发展心理学
作者
Gerarda Cappuccio,Margherita Lucia De Bernardi,A. Morlando,Cristina Peduto,Iris Scala,Michele Pinelli,Emanuele Bellacchio,Flavio Gioele Gallo,Adriano Magli,Carmen Plaitano,Mercedes Serrano,Leticia Pías,Jaume Català,Mercè Bolasell,Annalaura Torella,Vincenzo Nigro,Ginevra Zanni,Nicola Brunetti‐Pierri
摘要
Abstract Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X‐linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10 ‐related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10 , inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt‐bridge between Arg32 and Asp28. In addition to features consistent with RPL10‐ related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10 ‐related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.
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