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Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome.
Brain Dev. 2016 Mar; 38(3):337-40.BD

Abstract

BACKGROUND

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 1month 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.

Authors+Show Affiliations

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: miki.a@hama-med.ac.jp.Department of Pediatrics, Hamamatsu City Welfare and Medical Center for Development, Hamamatsu, Japan.Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26421802

Citation

Asahina, Miki, et al. "Novel RAB3GAP1 Compound Heterozygous Mutations in Japanese Siblings With Warburg Micro Syndrome." Brain & Development, vol. 38, no. 3, 2016, pp. 337-40.
Asahina M, Endoh Y, Matsubayashi T, et al. Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome. Brain Dev. 2016;38(3):337-40.
Asahina, M., Endoh, Y., Matsubayashi, T., Fukuda, T., & Ogata, T. (2016). Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome. Brain & Development, 38(3), 337-40. https://doi.org/10.1016/j.braindev.2015.09.006
Asahina M, et al. Novel RAB3GAP1 Compound Heterozygous Mutations in Japanese Siblings With Warburg Micro Syndrome. Brain Dev. 2016;38(3):337-40. PubMed PMID: 26421802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome. AU - Asahina,Miki, AU - Endoh,Yusaku, AU - Matsubayashi,Tomoko, AU - Fukuda,Tokiko, AU - Ogata,Tsutomu, Y1 - 2015/10/01/ PY - 2015/07/31/received PY - 2015/09/11/revised PY - 2015/09/12/accepted PY - 2015/10/1/entrez PY - 2015/10/1/pubmed PY - 2016/12/15/medline KW - Mutation KW - RAB3GAP1 KW - Warburg Micro syndrome SP - 337 EP - 40 JF - Brain & development JO - Brain Dev VL - 38 IS - 3 N2 - BACKGROUND: 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 1month 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. SN - 1872-7131 UR - https://www.unboundmedicine.com/medline/citation/26421802/Novel_RAB3GAP1_compound_heterozygous_mutations_in_Japanese_siblings_with_Warburg_Micro_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0387-7604(15)00205-3 DB - PRIME DP - Unbound Medicine ER -