New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish.
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New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. / Morris-Rosendahl, Deborah J; Segel, Reeval; Born, A Peter; Conrad, Christoph; Loeys, Bart; Brooks, Susan Sklower; Müller, Laura; Zeschnigk, Christine; Botti, Christina; Rabinowitz, Ron; Uyanik, Gökhan; Crocq, Marc-Antoine; Kraus, Uwe; Degen, Ingrid; Faes, Fran.
In: EUR J HUM GENET, Vol. 18, No. 10, 10, 2010, p. 1100-1106.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish.
AU - Morris-Rosendahl, Deborah J
AU - Segel, Reeval
AU - Born, A Peter
AU - Conrad, Christoph
AU - Loeys, Bart
AU - Brooks, Susan Sklower
AU - Müller, Laura
AU - Zeschnigk, Christine
AU - Botti, Christina
AU - Rabinowitz, Ron
AU - Uyanik, Gökhan
AU - Crocq, Marc-Antoine
AU - Kraus, Uwe
AU - Degen, Ingrid
AU - Faes, Fran
PY - 2010
Y1 - 2010
N2 - Warburg Micro Syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. We have found five new mutations in the RAB3GAP1 gene in seven patients with suspected Micro Syndrome from families with Turkish, Palestinian, Danish, and Guatemalan backgrounds. A thorough clinical investigation of the patients has allowed the delineation of symptoms that are consistently present in the patients and may aid the differential diagnosis of Micro Syndrome for patients in the future. All patients had postnatal microcephaly, micropthalmia, microcornia, bilateral congenital cataracts, short palpebral fissures, optic atrophy, severe mental retardation, and congenital hypotonia with subsequent spasticity. Only one patient had microcephaly at birth, highlighting the fact that congenital microcephaly is not a consistent feature of Micro syndrome. Analysis of the brain magnetic resonance imagings (MRIs) revealed a consistent pattern of polymicrogyria in the frontal and parietal lobes, wide sylvian fissures, a thin hypoplastic corpus callosum, and increased subdural spaces. All patients were homozygous for the mutations detected and all mutations were predicted to result in a truncated RAB3GAP1 protein. The analysis of nine polymorphic markers flanking the RAB3GAP1 gene showed that the mutation c.1410C>A (p.Tyr470X), for which a Danish patient was homozygous, occurred on a haplotype that is shared by the unrelated heterozygous parents of the patient. This suggests a possible founder effect for this mutation in the Danish population.
AB - Warburg Micro Syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. We have found five new mutations in the RAB3GAP1 gene in seven patients with suspected Micro Syndrome from families with Turkish, Palestinian, Danish, and Guatemalan backgrounds. A thorough clinical investigation of the patients has allowed the delineation of symptoms that are consistently present in the patients and may aid the differential diagnosis of Micro Syndrome for patients in the future. All patients had postnatal microcephaly, micropthalmia, microcornia, bilateral congenital cataracts, short palpebral fissures, optic atrophy, severe mental retardation, and congenital hypotonia with subsequent spasticity. Only one patient had microcephaly at birth, highlighting the fact that congenital microcephaly is not a consistent feature of Micro syndrome. Analysis of the brain magnetic resonance imagings (MRIs) revealed a consistent pattern of polymicrogyria in the frontal and parietal lobes, wide sylvian fissures, a thin hypoplastic corpus callosum, and increased subdural spaces. All patients were homozygous for the mutations detected and all mutations were predicted to result in a truncated RAB3GAP1 protein. The analysis of nine polymorphic markers flanking the RAB3GAP1 gene showed that the mutation c.1410C>A (p.Tyr470X), for which a Danish patient was homozygous, occurred on a haplotype that is shared by the unrelated heterozygous parents of the patient. This suggests a possible founder effect for this mutation in the Danish population.
KW - Humans
KW - Genetic Predisposition to Disease
KW - Magnetic Resonance Imaging
KW - Mutation
KW - Genetic Markers
KW - Abnormalities, Multiple genetics
KW - Mental Retardation genetics
KW - Hypogonadism genetics
KW - Arabs
KW - Brain abnormalities
KW - Cataract congenital
KW - Chromosomes, Human, Pair 2 genetics
KW - Cornea abnormalities
KW - Denmark
KW - Founder Effect
KW - Guatemala
KW - Microcephaly genetics
KW - Optic Atrophy genetics
KW - Turkey
KW - rab3 GTP-Binding Proteins genetics
KW - Humans
KW - Genetic Predisposition to Disease
KW - Magnetic Resonance Imaging
KW - Mutation
KW - Genetic Markers
KW - Abnormalities, Multiple genetics
KW - Mental Retardation genetics
KW - Hypogonadism genetics
KW - Arabs
KW - Brain abnormalities
KW - Cataract congenital
KW - Chromosomes, Human, Pair 2 genetics
KW - Cornea abnormalities
KW - Denmark
KW - Founder Effect
KW - Guatemala
KW - Microcephaly genetics
KW - Optic Atrophy genetics
KW - Turkey
KW - rab3 GTP-Binding Proteins genetics
M3 - SCORING: Zeitschriftenaufsatz
VL - 18
SP - 1100
EP - 1106
JO - EUR J HUM GENET
JF - EUR J HUM GENET
SN - 1018-4813
IS - 10
M1 - 10
ER -
