共查询到9条相似文献,搜索用时 0 毫秒
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Frederic Tran Mau-Them Marjolaine Willems Beate Albrecht Elodie Sanchez Jacques Puechberty Sabine Endele Anouck Schneider Nathalie Ruiz Pallares Chantal Missirian Francois Rivier Manon Girard Muriel Holder Sylvie Manouvrier Isabelle Touitou Genevieve Lefort Pierre Sarda Anne Moncla Severine Drunat Dagmar Wieczorek David Genevieve 《European journal of human genetics : EJHG》2014,22(2):289-292
Intellectual disability (ID) is frequent in the general population, with 1 in 50 individuals directly affected worldwide. The multiple etiologies include X-linked ID (XLID). Among syndromic XLID, few syndromes present severe ID associated with postnatal microcephaly and midline stereotypic hand movements. We report on three male patients with ID, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures (2/3), and non-inherited and postnatal onset microcephaly (2/3). Using array CGH and exome sequencing we characterised two truncating mutations in IQSEC2, namely two de novo intragenic duplication mapped to the Xp11.22 region and a nonsense mutation in exon 7. We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C. 相似文献
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Marie Vincent Corinne Collet Alain Verloes Laetitia Lambert Christian Herlin Catherine Blanchet Elodie Sanchez Séverine Drunat Jacqueline Vigneron Jean-Louis Laplanche Jacques Puechberty Pierre Sarda David Geneviève 《European journal of human genetics : EJHG》2014,22(1):52-56
Mandibulofacial dysostosis is part of a clinically and genetically heterogeneous group of disorders of craniofacial development, which lead to malar and mandibular hypoplasia. Treacher Collins syndrome is the major cause of mandibulofacial dysostosis and is due to mutations in the TCOF1 gene. Usually patients with Treacher Collins syndrome do not present with intellectual disability. Recently, the EFTUD2 gene was identified in patients with mandibulofacial dysostosis associated with microcephaly, intellectual disability and esophageal atresia. We report on two patients presenting with mandibulofacial dysostosis characteristic of Treacher Collins syndrome, but associated with unexpected intellectual disability, due to a large deletion encompassing several genes including the TCOF1 gene. We discuss the involvement of the other deleted genes such as CAMK2A or SLC6A7 in the cognitive development delay of the patients reported, and we propose the systematic investigation for 5q32 deletion when intellectual disability is associated with Treacher Collins syndrome. 相似文献
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Reza Asadollahi Beatrice Oneda Frenny Sheth Silvia Azzarello-Burri Rosa Baldinger Pascal Joset Beatrice Latal Walter Knirsch Soaham Desai Alessandra Baumer Gunnar Houge Joris Andrieux Anita Rauch 《European journal of human genetics : EJHG》2013,21(10):1100-1104
A chromosomal balanced translocation disrupting the MED13L (Mediator complex subunit13-like) gene, encoding a subunit of the Mediator complex, was previously associated with transposition of the great arteries (TGA) and intellectual disability (ID), and led to the identification of missense mutations in three patients with isolated TGA. Recently, a homozygous missense mutation in MED13L was found in two siblings with non-syndromic ID from a consanguineous family. Here, we describe for the first time, three patients with copy number changes affecting MED13L and delineate a recognizable MED13L haploinsufficiency syndrome. Using high resolution molecular karyotyping, we identified two intragenic de novo frameshift deletions, likely resulting in haploinsufficiency, in two patients with a similar phenotype of hypotonia, moderate ID, conotruncal heart defect and facial anomalies. In both, Sanger sequencing of MED13L did not reveal any pathogenic mutation and exome sequencing in one patient showed no evidence for a non-allelic second hit. A further patient with hypotonia, learning difficulties and perimembranous VSD showed a 1 Mb de novo triplication in 12q24.2, including MED13L and MAP1LC3B2. Our findings show that MED13L haploinsufficiency in contrast to the previously observed missense mutations cause a distinct syndromic phenotype. Additionally, a MED13L copy number gain results in a milder phenotype. The clinical features suggesting a neurocristopathy may be explained by animal model studies indicating involvement of the Mediator complex subunit 13 in neural crest induction. 相似文献
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3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability,epilepsy and stereotypic behavior
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Nicola Dikow Bianca Maas Stephanie Karch Martin Granzow Johannes W.G. Janssen Anna Jauch Katrin Hinderhofer Christian Sutter Susanne Schubert‐Bast Britt Marie Anderlid Bruno Dallapiccola Nathalie Van der Aa Ute Moog 《American journal of medical genetics. Part A》2014,164(12):3061-3068
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Karijn Floor Tuva Barøy Doriana Misceo Øivind J. Kanavin Madeleine Fannemel Eirik Frengen 《European journal of medical genetics》2012,55(12):695-699
We report a 11 year old male patient ascertained for mild intellectual disability and minor dysmorphic features, carrying a 1 Mb de novo deletion on chromosome 11q13.1q13.2 detected by aCGH. This is the first report of a deletion in this region in a patient presenting with intellectual impairment and mild dysmorphic traits. The 1 Mb deleted area encompasses 47 RefSeq genes, including Cornichon homologue 2 (CNIH2), Cofilin-1 (CFL1) and neuronal PAS domain-containing protein 4 (NPAS4), which are highly expressed in the central nervous system. Knockout of the CNIH2 and CFL1 orthologues in animals results in migration disturbances, while low or no expression of Npas4 in mice results in impairment of memory and learning. These three genes have previously been suggested as candidate genes for neurological disorders. 相似文献
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Zafar Iqbal Mohsin Shahzad Lisenka E L M Vissers Monique van Scherpenzeel Christian Gilissen Attia Razzaq Muhammad Yasir Zahoor Shaheen N Khan Tjitske Kleefstra Joris A Veltman Arjan P M de Brouwer Dirk J Lefeber Hans van Bokhoven Sheikh Riazuddin 《European journal of human genetics : EJHG》2013,21(8):844-849
Congenital disorders of glycosylation (CDG) are a large group of recessive multisystem disorders caused by impaired protein or lipid glycosylation. The CDG-I subgroup is characterized by protein N-glycosylation defects originating in the endoplasmic reticulum. The genetic defect is known for 17 different CDG-I subtypes. Patients in the few reported DPAGT1-CDG families exhibit severe intellectual disability (ID), epilepsy, microcephaly, severe hypotonia, facial dysmorphism and structural brain anomalies. In this study, we report a non-consanguineous family with two affected adults presenting with a relatively mild phenotype consisting of moderate ID, epilepsy, hypotonia, aggressive behavior and balance problems. Exome sequencing revealed a compound heterozygous missense mutation, c.85A>T (p.I29F) and c.503T>C (p.L168P), in the DPAGT1 gene. The affected amino acids are located in the first and fifth transmembrane domains of the protein. Isoelectric focusing and high-resolution mass spectrometry analyses of serum transferrin revealed glycosylation profiles that are consistent with a CDG-I defect. Our results show that the clinical spectrum of DPAGT1-CDG is much broader than appreciated so far. 相似文献