Paediatric pseudo-obstruction syndrome
Gene: LMOD1
The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 7:44 a.m. | Last Modified: 1 Feb 2023, 7:44 a.m.
Panel Version: 0.216
Comment on classification of this gene: This gene should be rated GREEN, as this gene has been implicated in megacystis microcolon intestinal hypoperistalsis syndrome in two unrelated patients and is supported by evidence from mouse model.
A dutch female infant identified with homozygous nonsense variant (p.R370X) died at 5 days of life. Both her parents were heterozygous for the same variant. The clinical presentations include distended and lax abdominal wall, with palpable intestines, bladder distention, bilateral distention of the proximal ureters, and hydronephrosis (PMID:28292896).
A male infant with compound heterozygous missense variants (p.T369M; p.R421H) was also presented with typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon (PMID:35170814).
A mouse model with a similar Lmod1 mutation, engineered with CRISPR-Cas9 genome editing, exhibited the same gastrointestinal and urinary bladder phenotypes as seen in the dutch female infant (PMID:28292896).
This gene-disease association has already been reported in OMIM.Created: 21 Dec 2022, 2:56 p.m. | Last Modified: 21 Dec 2022, 2:58 p.m.
Panel Version: 0.73
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, OMIM:619362
Publications
Review submitted on behalf of Dr. Anna Rybak and Dr. Osvaldo Borreli, Great Ormond Street Hospital for Children NHS Foundation Trust. Gene group: Myopathic PIPO/MMIHS. Protein function: Encodes visceral smooth muscle cells.Created: 20 Dec 2022, 3:32 p.m. | Last Modified: 20 Dec 2022, 3:32 p.m.
Panel Version: 0.2
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Abnormal LMOD1 leads to impaired intestinal smooth muscle contractility
Publications
Publications for gene: LMOD1 were set to
Phenotypes for gene: LMOD1 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, OMIM:619362
Mode of inheritance for gene: LMOD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: lmod1 has been classified as Green List (High Evidence).
gene: LMOD1 was added gene: LMOD1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list Mode of inheritance for gene: LMOD1 was set to