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Intellectual disability
Gene: HTT

HTT (huntingtin)
EnsemblGeneIds (GRCh38): ENSG00000197386
EnsemblGeneIds (GRCh37): ENSG00000197386
OMIM: 613004, Gene2Phenotype
HTT is in 17 panels

4 reviews

Eleanor Williams (Genomics England Curator)

PMID: 33432339 - Jung et al 2021 - further characterisation of the family previously reported in PMID: 27329733 (Rodan et al 2016) - using WGS they confirm they are the most likely cause of the LOMARS phenotype and clarify their locations as NM_002111.8(HTT): c.8157T>A (p.Phe2719Leu) and NM_002111.8(HTT)c.4469+1G>A (Note there are incorrect Clinvar entries). Functional studies show them each to be a hypomorphic mutation, resulting in severe deficiency of huntingtin in compound heterozygotes.

Still only 2 cases reported to date (PMID: 27329733/33432339 and 26740508) with biallelic LOF variants in HTT associated with the LOMARS phenotype although this study add further weight with some functional data.
Created: 4 May 2021, 2:09 p.m. | Last Modified: 4 May 2021, 2:15 p.m.

Panel Version: 3.1056

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lopes-Maciel-Rodan syndrome OMIM:617435

Publications

33432339

Created: 4 May 2021, 2:09 p.m.
Last Modified: 4 May 2021, 2:15 p.m.
Panel version: 3.1056

Ellen McDonagh (Genomics England Curator)

For the ID panel, Lopes-Maciel-Rodan syndrome is relevant and not Huntington Disease. Two unrelated families currently reported for Lopes-Maciel-Rodan syndrome, therefore rating status made amber at this time and added the 'watchlist' tag in case further cases are reported. If this gene were to become green, it is SNVs that should be reported for Lopes-Maciel-Rodan syndrome, and not expansion repeats which cause Huntington disease. Not in Gene2Phenotype gene lists.

Created: 19 Sep 2017, 8:38 a.m.

Comment on mode of inheritance: Biallelic SNVs have been reported for Lopes-Maciel-Rodan syndrome.
Created: 19 Sep 2017, 7:57 a.m.

Created: 19 Sep 2017, 7:58 a.m.

Panel version: 1.414

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : NA
Created: 27 Jul 2017, 6:43 p.m.

Evidences key, gene present in following gene lists and main mutation mechanism : manju_list; UKGTN_v12; neuro_20160418_strict; NA. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Personal communication with NIHRBRRD BRIDGE SPEED
Version 12 ukgtn.nhs.uk

Created: 2 Aug 2017, 7:12 p.m.

Panel version: 1.354

Louise Daugherty (Genomics England Curator)

I don't know

Clinical presentation significantly overlapping Rett syndrome (RTT) often presenting with severe intellectual disability (ID). LOMARS is an autosomal recessive neurodevelopmental disorder characterized by developmental regression in infancy, delayed psychomotor development, severe intellectual disability, and cerebral and cerebellar atrophy. Additional features include swallowing problems, dystonia, bradykinesia, and continuous manual stereotypies without chorea. Some patients manifest seizures.To date only 4 patients from two unrelated families have been reported in the literature with Lopes-Maciel-Rodan syndrome caused by variants in HTT.
Created: 5 Jan 2018, 2:42 p.m.

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.
Created: 20 Jul 2017, noon

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lopes-Maciel-Rodan syndrome, 617435; LOMARS; Intellectual disability

Publications

Created: 20 Jul 2017, noon

Panel version: 1.567

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber

Phenotypes

Lopes-Maciel-Rodan syndrome, OMIM:617435
LOMARS

Tags

watchlist

OMIM

613004

Clinvar variants

Variants in HTT

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

10 Nov 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: HTT were set to 26740508; 27329733

10 Nov 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: HTT were changed from Lopes-Maciel-Rodan syndrome, 617435; LOMARS; Intellectual disability to Lopes-Maciel-Rodan syndrome, OMIM:617435; LOMARS

12 Mar 2018, Gel status: 2