Early onset or syndromic epilepsy
Gene: ATRX
See XLD and XLR inheritanceCreated: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
XLD alpha thalassemia/mental retardation syndrome - 35% of cases seizures reported. XLR mental-retardation-hypotonic facies syndrome - 35% of cases seizures reported. Lots of reported mutations on HGMD Pro - missense, nonsense, splicing, small dels/ins and gross del/ins.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Alpha-thalassemia myelodysplasia syndrome, somatic, 300448; Alpha-thalassemia/mental retardation syndrome, 301040; Mental retardation-hypotonic facies syndrome, X-linked,309580
Publications
Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on Post-Webex review by Helen Lord.Created: 7 Sep 2019, 10:37 a.m. | Last Modified: 7 Sep 2019, 10:37 a.m.
Panel Version: 1.272
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
PMID:16955409: Badens et al. 2006 report a 4 year old female with a heterozygous R246C variant in ATRX and a skewed pattern of X-inactivation where her maternally-inherited X chromosome that carried the de novo variant remained active. Clinical features included severed DD. Epilepsy/seizures were not reported amongst her phenotypes.Created: 22 Jul 2019, 8:05 a.m. | Last Modified: 22 Jul 2019, 8:05 a.m.
Panel Version: 1.171
PMID:25606380: Moncini et al 2013 report 2 brothers with features including moderate ID and seizures. The ATRX c.109C>T (p.R37X) variant was present in both brothers, and the mother was a healthy carrier.Created: 18 Jul 2019, 4:04 p.m. | Last Modified: 18 Jul 2019, 4:04 p.m.
Panel Version: 1.169
Comment on mode of inheritance: After discussion with reviewer, this should be biallelic (recessive). This is also confirmed in gene2phenotype with a hemizygous mode of inheritance.Created: 17 Dec 2015, 12:49 p.m.
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:50 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:13 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:04 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 12:26 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: atrx has been classified as Green List (High Evidence).
Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked to Alpha-thalassemia/mental retardation syndrome, 301040; Mental retardation-hypotonic facies syndrome, X-linked, 309580
Mode of inheritance for gene: ATRX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ATRX were set to 25606380; 11449489; 7697714; 11050622
Source Wessex and West Midlands GLH was added to ATRX.
Source NHS GMS was added to ATRX.
Publications for gene: ATRX were set to 25606380: 11449489; 7697714; 11050622
Publications for gene: ATRX were set to Gibbons et al (1995) Cell 80: 837-845; Stevenson et al (2000) Am J Med Genet 94: 383-385
Richard Scott: Where females manifest it woul
Victorian Clinical Genetics Services was added to ATRX. Panel: Genetic Epilepsy Syndromes
ATRX was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,UKGTN
ATRX was created by Sarah Leigh