https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 A non-coding variant in the 5ʹ UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:42920 Wed 07 Sep 2022 13:13:35 AEST ]]> Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9647 Sat 24 Mar 2018 08:35:25 AEDT ]]> Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10275 Sat 24 Mar 2018 08:13:04 AEDT ]]> Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10419 A) in a published family with nonsyndromic MR, MRX13. This change occurs in a highly conserved amino acid, with proline (P) being substituted by threonine (T) (p.P544T). Functional analysis shows that this amino-acid substitution compromises both tri- and didemethylase activity of the JARID1C protein. We conclude that the two novel changes impair JARID1C protein function and are disease-causing mutations in these families.]]> Sat 24 Mar 2018 08:12:38 AEDT ]]> CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10278 T) in two small families with nystagmus and MR. Detailed clinical examinations of all six families, including an ophthalmological review in four families, were undertaken to further characterise the phenotype. We report on the clinical features of 24 individuals, mostly male, from six families with CASK mutations. The phenotype was variable, ranging from non-syndromic mild MR to severe MR associated with microcephaly and dysmorphic facial features. Carrier females were variably affected. Congenital nystagmus was found in members of four of the families. Our findings reinforce the CASK gene as a relatively frequent cause of XLMR in females and males. We further define the phenotypic spectrum and demonstrate that affected males with missense mutations or in-frame deletions in CASK are frequently associated with congenital nystagmus and XLMR, a striking feature not previously reported.]]> Sat 24 Mar 2018 08:09:09 AEDT ]]> Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5122 Sat 24 Mar 2018 07:48:57 AEDT ]]> Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5093 Sat 24 Mar 2018 07:48:50 AEDT ]]> MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4978 2.0, 401 male MR sibships and 47 sporadic male patients with AHDS-like clinical features. One nonsense mutation (c.629insA) and two missense changes (c.1A>T and c.1673G>A) were identified. Consistent with previous reports on MCT8 missense changes, the patient with c.1673G>A showed elevated serum T3 level. The c.1A>T change in another patient affects a putative translation start codon, but the same change was present in his healthy brother. In addition normal serum T3 levels were present, suggesting that the c.1A>T (NM_006517) variation is not responsible for the MR phenotype but indicates that MCT8 translation likely starts with a methionine at position p.75. Moreover, we characterized a de novo translocation t(X;9)(q13.2;p24) in a female patient with full blown AHDS clinical features including elevated serum T3 levels. The MCT8 gene was disrupted at the X-breakpoint. A complete loss of MCT8 expression was observed in a fibroblast cell-line derived from this patient because of unfavorable nonrandom X-inactivation. Taken together, these data indicate that MCT8 mutations are not common in non-AHDS MR patients yet they support that elevated serum T3 levels can be indicative for AHDS and that AHDS clinical features can be present in female MCT8 mutation carriers whenever there is unfavorable nonrandom X-inactivation.]]> Sat 24 Mar 2018 07:46:52 AEDT ]]> SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5320 Sat 24 Mar 2018 07:45:58 AEDT ]]> Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:276 30% of mutations seem to cluster on proximal Xp and in the pericentric region. In a systematic screen of brain-expressed genes from this region in 210 families with XLMR, we identified seven different mutations in JARID1C, including one frameshift mutation and two nonsense mutations that introduce premature stop codons, as well as four missense mutations that alter evolutionarily conserved amino acids. In two of these families, expression studies revealed the almost complete absence of the mutated JARID1C transcript, suggesting that the phenotype in these families results from functional loss of the JARID1C protein. JARID1C (Jumonji AT-rich interactive domain 1C), formerly known as "SMCX," is highly similar to the Y-chromosomal gene JARID1D/SMCY, which encodes the H-Y antigen. The JARID1C protein belongs to the highly conserved ARID protein family. It contains several DNA-binding motifs that link it to transcriptional regulation and chromatin remodeling, processes that are defective in various other forms of mental retardation. Our results suggest that JARID1C mutations are a relatively common cause of XLMR and that this gene might play an important role in human brain function.]]> Sat 24 Mar 2018 07:43:03 AEDT ]]> Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3341 Sat 24 Mar 2018 07:22:35 AEDT ]]> A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24614 T, p.Q301*). The mutation segregated with the disease in the family and was not observed in over 100 000 control X chromosomes. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals. Conclusions: The association of RNF113A mutation with non-photosensitive TTD identifies a new locus for these disorders on the X chromosome. The extended phenotype within this family includes panhypopituitarism, cutis marmorata and congenital short oesophagus.]]> Sat 24 Mar 2018 07:11:55 AEDT ]]>