Paediatric pseudo-obstruction syndrome

Gene: MYLK

Green List (high evidence)

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 rating: The rating should be GREEN as this gene has been implicated in Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (MIM #249210) from two unrelated cases, and supported by results from functional studies.

Two families were identified with homozygous variants (7bp deletion in one family and putative splice-site variant in other) and were reported with the death of 5 children with MMIHS from these families (PMID:28602422). In addition, the existence of a conditional-Mylk-knockout mouse model with severe gut dysmotility and abnormal function of the bladder supports this gene-disease association.

This gene-disease association has already been reported in both OMIM and G2P.

Created: 29 Dec 2022, 7:44 p.m. | Last Modified: 29 Dec 2022, 7:44 p.m.

Panel Version: 0.93

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Megacystis-microcolon-intestinal hypoperistalsis syndrome 1, OMIM:249210

Publications

• 28602422
• 31848803
• 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 kinase required for myosin activation and subsequent interaction with actin filaments.

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 MYLK leads to impaired smooth muscle cell contraction

Publications

• 33729000
• 31848803