Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome

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• 作者：Miki Asahina^a ; ^{miki.a@hama-med.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yusaku Endoh^b ; Tomoko Matsubayashi^a ; Tokiko Fukuda^a ; Tsutomu Ogata^a
• 关键词：Warburg Micro syndrome ; RAB3GAP1 ; Mutation
• 刊名：Brain and Development
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：38
• 期：3
• 页码：337-340
• 全文大小：523 K

文摘

Warburg Micro syndrome (WARBM) is a rare autosomal recessive disease characterized by postnatal growth retardation, microcephaly, severely delayed motor and intellectual development, microcornea, congenital cataracts, optic atrophy, and hypogonadism. While WARBM is a genetically heterogeneous condition, RAB3GAP1 mutations account for ∼40% of WARBM patients, and 69 different mutations of various types (nonsense, missense, frameshift, and splice site mutations) have been identified to date.

Patients

Japanese siblings (a 7 years 3 months old male and a 2 years 1 month old female) were found to have WARBM-compatible phenotypes. Direct sequencing of RAB3GAP1 revealed novel compound heterozygous mutations in the siblings: a paternally inherited missense mutation (c.560G > C; p.Arg187Pro) in exon 7 and a maternally derived nonsense mutation (c.1009C > T; p.Arg337Ter) in exon 12.

Conclusion

The siblings had WARBM caused by novel mutations in RAB3GAP1. Since molecular diagnosis permits adequate genetic counseling and appropriate management for predicted complications such as adequate sex steroid supplementation therapy for hypogonadism, in addition to standard supportive therapies for developmental delay and visual dysfunction, we recommend molecular studies for this rare condition.