Early onset or syndromic epilepsy

Gene: ATRX

Green List (high evidence)

See XLD and XLR inheritance

Created: 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)

Green List (high evidence)

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

• 16722615

I don't know

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.

Green List (high evidence)

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

• Gibbons et al (1995) Cell 80: 837-845
• Stevenson et al (2000) Am J Med Genet 94: 383-385

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

• Gibbons et al (1995) Cell 80: 837-845
• Stevenson et al (2000) Am J Med Genet 94: 383-385

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

• Gibbons et al (1995) Cell 80: 837-845
• Stevenson et al (2000) Am J Med Genet 94: 383-385

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

• Gibbons et al (1995) Cell 80: 837-845
• Stevenson et al (2000) Am J Med Genet 94: 383-385

Variants in this GENE are reported as part of current diagnostic practice