Abnormal facies, cleft palate, and generalized dysostosis: A lethal X-linked syndrome

André, Marli Eliza Dalmazo Afonso de; Vigneron, Jacqueline; Didier, F

doi:10.1016/s0022-3476(81)80835-9

Cited by 31 publications

(23 citation statements)

References 9 publications

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“…Survivorship is associated with neurodevelopmental delay, but this is not invariable. 16 Female carriers have a subclinical bone dysplasia and facial dysmorphism, but can occasionally manifest a more severe phenotype. 18 Clinical discrimination from a female carrier with a mutation associated with OPD1 in a singleton female case is unreliable.…”

Section: Otopalatodigital Syndrome Typementioning

confidence: 99%

Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome

Robertson

2006

Eur J Hum Genet

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Section: Otopalatodigital Syndrome Typementioning

confidence: 99%

Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome

Robertson

2006

Eur J Hum Genet

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“…individuals with mutations in FLNA associated with OPD-spectrum disorders do not have a higher prevalence of seizures or the characteristic phenotypic features of PVNH 26,27 . Second, 12 of 14 mutations causing PVNH predict protein truncation and/or mRNA instability and are assumed to lead to loss of function 3,5,6 , whereas 17 of 17 mutations causing OPD-spectrum disorders conserve the reading frame, compatible with specific altered functions.…”

mentioning

confidence: 95%

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans

et al. 2003

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Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers 1,2 . We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development.

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“…Another patient had a 586C to G mutation, leading to an Arg196Gly substitution in filamin A (Robertson et al 2003). Andre et al (1981) originally reported that the family of the patient had had four other cases of OPD II, all of which were severe, with the patients dying at 21 days to 3.5 months after birth. Thus, the phenotype-genotype correlation was not apparent in the three OPD patients with a mutation at 586C in FLNA: the identical mutation (C586T) can give rise to two distinct phenotypes, OPD I and OPD II.…”

Section: Discussionmentioning

confidence: 99%

A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype–genotype correlation

et al. 2007

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We report the case of a 12 year-old boy with oto-palato-digital syndrome type II (OPD II). He had various anomalies at birth, including bilateral cataracts, bilateral glaucoma, bilateral severe hearing impairment, congenital heart defect, umbilical herniation, bowed extremities and constrictions of various joints. These clinical features and whole body X-ray findings were compatible with OPD II. However, his ocular disorders such as congenital cataract and glaucoma, and congenital heart defect have never been associated with OPD II as far as we know. His chromosomal analysis revealed normal karyotype, 46,XY. Analysis of the filamin A gene using a standard PCRdirect sequencing method determined a C586T (Arg196Trp) missense mutation in exon 3. Interestingly, the same C586T mutation was reported previously in a patient with OPD I (mild form). Thus, phenotype-genotype correlation of OPD is lacking in those patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes, or to identify other factor(s) that influence the clinical features of this syndrome.

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Abnormal facies, cleft palate, and generalized dysostosis: A lethal X-linked syndrome

Cited by 31 publications

References 9 publications

Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome

Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans

A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype–genotype correlation

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