Paediatric pseudo-obstruction syndrome

Gene: TTC7A

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 list classification: This gene can be rated GREEN as this gene has been implicated in gastrointestinal disorders, as reported in >3 unrelated cases from multiple studies.

TTC7A is associated with gastrointestinal defects and immunodeficiency syndrome (MIM #243150) in OMIM and intestinal atresia, multiple in G2P.

TTC7A-associated syndrome displays a broad phenotypic spectrum. It is characterised by multiple intestinal atresia, in which atresia occurs at various levels throughout the small and large intestines. Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency.

Among the seven patients reported in PMID:34985046, four patients had epithelial abnormalities, five had multiple intestinal atresias, SCID in four patients and enterocolitis/ VEO-IBD in two patients. PMID:35627206 also reported a child with multiple intestinal atresia with combined immune deficiency (MIA-CID) and this patient displayed a homozygous missense variant c.295A>G (p.M99V). A patient from PMID:31787977 was reported with recurrent lymphoproliferative syndrome and pan-hypergammaglobulinemia associated with chronic intestinal pseudo-obstruction (CIPO) and displayed autosomal recessive c.974G>A (p.R325Q) variant in the TTC7A gene.

Created: 2 Jan 2023, 7:45 p.m. | Last Modified: 2 Jan 2023, 7:45 p.m.

Panel Version: 0.156

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Gastrointestinal defects and immunodeficiency syndrome, OMIM:243150

Publications

• 31787977
• 34975848
• 34985046
• 35627206

Review submitted on behalf of Dr. Anna Rybak and Dr. Osvaldo Borreli, Great Ormond Street Hospital for Children NHS Foundation Trust. Gene group: Other. Protein function: Member of the tetratricopeptide repeat family and is thought to interact with the components of many different macromolecular complexes.. Other information: TTC7A novel c.974G>A (p.R325Q) mutation.

Created: 20 Dec 2022, 3:32 p.m. | Last Modified: 20 Dec 2022, 3:32 p.m.

Panel Version: 0.2

Mode of inheritance
Unknown

Phenotypes
Lymphoproliferative syndrome and hypergammaglobulinemia and/or chronic intestinal pseudo-obstruction.

Publications

• 31787977