Tags

Type your tag names separated by a space and hit enter

A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome.
Hum Genet. 2011 Jan; 129(1):45-50.HG

Abstract

Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay. The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common. While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome. Here, we report a novel homozygous RAB3GAP2 small in-frame deletion, c.499_507delTTCTACACT (p.Phe167_Thr169del) that causes Warburg Micro syndrome in a girl from a consanguineous Turkish family presenting with congenital cataracts, microphthalmia, absent visually evoked potentials, microcephaly, polymicrogyria, hypoplasia of the corpus callosum, and severe developmental delay. No RAB3GAP2 mutations were detected in ten additional unrelated patients with RAB3GAP1-negative Warburg Micro syndrome, consistent with further genetic heterogeneity. In conclusion, we provide evidence that RAB3GAP2 mutations are not specific to Martsolf syndrome. Rather, our findings suggest that loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype. Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the "Warburg-Martsolf syndrome") which is presumably determined by the mutant gene and the nature of the mutation.

Authors+Show Affiliations

Institute of Human Genetics, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany. guntram.borck@uk-koeln.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20967465

Citation

Borck, Guntram, et al. "A Homozygous RAB3GAP2 Mutation Causes Warburg Micro Syndrome." Human Genetics, vol. 129, no. 1, 2011, pp. 45-50.
Borck G, Wunram H, Steiert A, et al. A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum Genet. 2011;129(1):45-50.
Borck, G., Wunram, H., Steiert, A., Volk, A. E., Körber, F., Roters, S., Herkenrath, P., Wollnik, B., Morris-Rosendahl, D. J., & Kubisch, C. (2011). A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Human Genetics, 129(1), 45-50. https://doi.org/10.1007/s00439-010-0896-2
Borck G, et al. A Homozygous RAB3GAP2 Mutation Causes Warburg Micro Syndrome. Hum Genet. 2011;129(1):45-50. PubMed PMID: 20967465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. AU - Borck,Guntram, AU - Wunram,Heidrun, AU - Steiert,Angela, AU - Volk,Alexander E, AU - Körber,Friederike, AU - Roters,Sigrid, AU - Herkenrath,Peter, AU - Wollnik,Bernd, AU - Morris-Rosendahl,Deborah J, AU - Kubisch,Christian, Y1 - 2010/10/22/ PY - 2010/08/23/received PY - 2010/09/25/accepted PY - 2010/10/23/entrez PY - 2010/10/23/pubmed PY - 2011/2/3/medline SP - 45 EP - 50 JF - Human genetics JO - Hum Genet VL - 129 IS - 1 N2 - Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay. The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common. While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome. Here, we report a novel homozygous RAB3GAP2 small in-frame deletion, c.499_507delTTCTACACT (p.Phe167_Thr169del) that causes Warburg Micro syndrome in a girl from a consanguineous Turkish family presenting with congenital cataracts, microphthalmia, absent visually evoked potentials, microcephaly, polymicrogyria, hypoplasia of the corpus callosum, and severe developmental delay. No RAB3GAP2 mutations were detected in ten additional unrelated patients with RAB3GAP1-negative Warburg Micro syndrome, consistent with further genetic heterogeneity. In conclusion, we provide evidence that RAB3GAP2 mutations are not specific to Martsolf syndrome. Rather, our findings suggest that loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype. Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the "Warburg-Martsolf syndrome") which is presumably determined by the mutant gene and the nature of the mutation. SN - 1432-1203 UR - https://www.unboundmedicine.com/medline/citation/20967465/A_homozygous_RAB3GAP2_mutation_causes_Warburg_Micro_syndrome_ L2 - https://dx.doi.org/10.1007/s00439-010-0896-2 DB - PRIME DP - Unbound Medicine ER -