Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

17q11.2 microduplication syndrome is a recently described relatively rare condition associated with a nonspecific phenotype. Intellectual disability, developmental delay, and dysmorphisms are the only clinical features common to a majority of cases. Seventeen patients have been reported so far. Here, we present another patient with 17q11.2 duplication and no signs of neurofibromatosis type 1, identified by array-CGH. We compared clinical features and genetic data with those of previously reported patients with 17q11.2 microduplications. We also analyzed the gene content of the duplicated region in order to investigate the possible role of specific genes in the clinical phenotype of our patient.

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Expanding the clinical phenotype at the 3q13.31 locus with a new case of microdeletion and first characterization of the reciprocal duplication

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2013.07.013 ◽

2013 ◽

Vol 110 (1-2) ◽

pp. 90-97 ◽

Cited By ~ 10

Author(s):

Marie-Laure Vuillaume ◽

Marie-Ange Delrue ◽

Sophie Naudion ◽

Jérôme Toutain ◽

Patricia Fergelot ◽

...

Keyword(s):

Clinical Phenotype

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NF1 microdeletion syndrome: a phenotypical characterization of a rare case of neurofibromatosis type 1

Acta Dermatovenerologica Alpina Pannonica et Adriatica ◽

10.15570/actaapa.2020.20 ◽

2020 ◽

Vol 29 (2) ◽

Author(s):

Jorge Lopes ◽

Diogo Teixeira ◽

Cristina Sousa ◽

Armando Baptista ◽

Eduarda Osório Ferreira

Keyword(s):

Neurofibromatosis Type 1 ◽

Rare Case ◽

Neurofibromatosis Type ◽

Microdeletion Syndrome ◽

Nf1 Microdeletion Syndrome

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Comparative characterization of PCDH19 missense and truncating variants in PCDH19-related epilepsy

Journal of Human Genetics ◽

10.1038/s10038-020-00880-z ◽

2020 ◽

Author(s):

Mami Shibata ◽

Atsushi Ishii ◽

Ayako Goto ◽

Shinichi Hirose

Keyword(s):

Distribution Function ◽

Intellectual Disability ◽

Cumulative Distribution Function ◽

Clinical Phenotype ◽

Cytoplasmic Domain ◽

Cumulative Distribution ◽

Clinical Implications ◽

Healthy Individuals ◽

Conserved Domains

AbstractMissense and truncating variants in protocadherin 19 (PCDH19) cause PCDH19-related epilepsy. In this study, we aimed to investigate variations in distributional characteristics and the clinical implications of variant type in PCDH19-related epilepsy. We comprehensively collected PCDH19 missense and truncating variants from the literature and by sequencing six exons and intron–exon boundaries of PCDH19 in our cohort. We investigated the distribution of each type of variant using the cumulative distribution function and tested for associations between variant types and phenotypes. The distribution of missense variants in patients was clearly different from that of healthy individuals and was uniform throughout the extracellular cadherin (EC) domain, which consisted of six highly conserved domains. Truncating variants showed two types of distributions: (1) located from EC domain 1 to EC domain 4, and (2) located from EC domain 5 to the cytoplasmic domain. Furthermore, we also found that later onset seizures and milder intellectual disability occurred in patients with truncating variants located from EC domain 5 to the cytoplasmic domain compared with those of patients with other variants. Our findings provide the first evidence of two types of truncating variants in the PCDH19 gene with regard to distribution and the resulting clinical phenotype.

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Genetic characterization of Stargardt clinical phenotype in South Indian patients using sanger and targeted sequencing

Eye and Vision ◽

10.1186/s40662-019-0168-8 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Rajendran Kadarkarai Raj ◽

Pankaja Dhoble ◽

Rupa Anjanamurthy ◽

Prakash Chermakani ◽

Manojkumar Kumaran ◽

...

Keyword(s):

Clinical Phenotype ◽

South Indian Population ◽

Missense Mutations ◽

Stargardt Disease ◽

Fundus Imaging ◽

South Indian ◽

Base Pair Deletion ◽

Single Base Pair ◽

Larger Sample

Abstract Background Stargardt disease 1 (STGD1; MIM 248200) is a monogenic form of autosomal recessive genetic disease caused by mutation in ABCA4. This gene has a major role in hydrolyzing N-retinylidene-phosphatidylethanolamine to all-trans-retinal and phosphatidylethanolamine. The purpose of this study is to identify the frequency of putative disease-causing mutations associated with Stargardt disease in a South Indian population. Methods A total of 28 clinically diagnosed Stargardt-like phenotype patients were recruited from south India. Ophthalmic examination of all patients was carefully carried out by a retina specialist based on the stages of fundus imaging and ERG grouping. Genetic analysis of ABCA4 was performed for all patients using Sanger sequencing and clinical exome sequencing. Results This study identified disease-causing mutations in ABCA4 in 75% (21/28) of patients, 7% (2/28) exhibited benign variants and 18% (5/28) were negative for the disease-causing mutation. Conclusion This is the first study describing the genetic association of ABCA4 disease-causing mutation in South Indian Stargardt 1 patients (STGD1). Our findings highlighted the presence of two novel missense mutations and an (in/del, single base pair deletion & splice variant) in ABCA4. However, genetic heterogeneity in ABCA4 mutants requires a larger sample size to establish a true correlation with clinical phenotype.

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