Paediatric pseudo-obstruction syndrome

Gene: MYL9

Comment on list classification: There is now sufficient evidence to rate this gene as Green at the next GMS panel update.

Created: 9 May 2023, 1:37 p.m. | Last Modified: 9 May 2023, 1:37 p.m.

Panel Version: 1.3

Third family reported by Billon et al. 2020 (PMID: 32621347) with the same homozygous exon 4 deletion of MYL9 as the one detected by Moreno et al. 2018 (PMID: 29453416 / 27481187) in an unrelated case. Family includes three sibs affected with megacystis, intestinal malrotation, small and thin colon, as well as some dysmorphic features. Fetopathological examination confirmed the diagnosis of MMIHS.

Possibly fourth family in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641

Created: 9 May 2023, 1:36 p.m. | Last Modified: 9 May 2023, 1:36 p.m.

Panel Version: 1.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365

Publications

• 29453416
• 33031641
• 32621347
• 33264186

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 12:19 p.m. | Last Modified: 6 Dec 2024, 12:19 p.m.

Panel Version: 1.7

The rating of this gene has been updated to Amber 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 rating: The rating should be AMBER as this gene has been implicated in Megacystis-microcolon-intestinal hypoperistalsis syndrome 4 (MIM #619365) from two unrelated cases.

A homozygous deletion variant that removes exon 4 and a compound heterozygous variant that removes exon 4 on one allele and causing a 9bp deletion that removes canonical splice donor site at exon 2 from the second allele were reported.

This gene-disease association has already been reported in OMIM.

Created: 29 Dec 2022, 7:26 p.m. | Last Modified: 29 Dec 2022, 7:26 p.m.

Panel Version: 0.89

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365

Publications

• 27481187
• 31848803
• 33031641
• 33729000

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 a regulatory myosin light chain.

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 MYL9 leads to impaired intestinal smooth muscle contractility

Publications

• 33729000
• 31848803