Severe microcephaly

Gene: PUS7

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

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

Green List (high evidence)

Comment on list classification: Promoting from grey to amber but with a recommendation for a green rating following GMS review. 4 families reported with a severe microcephaly phenotype.

Created: 19 May 2021, 4:48 p.m. | Last Modified: 19 May 2021, 4:48 p.m.

Panel Version: 2.178

Associated with Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature #618342 (AR) in OMIM.

4 families reported in which a severe microcephaly phenotype was observed along with intellectual disability.

PMID:30526862 - de Brouwer et al 2018 - report 6 individuals from 3 families with 3 different homozygous protein truncating variants in PUS7. All presented with intellectual disability with speech delay, short stature, microcephaly, and aggressive behaviour. In 3 individuals from 2 families the head circumference was more than -3 SD from normal.

PMID:30778726 - Shaheen et al 2019 - report 3 individuals from 2 consanguineous families with homozygous PUS7 variants (missense and frameshift deletion) and a phenotype which includes intellectual disability and progressive microcephaly. The microcephaly was severe in all 3 individuals (OFC −4.5SD at age 8, −5.7 SD at age 4.5 and −5.2 SD at age 2.5 years). The variants segregated with the phenotype in both families.

PMID:31583274 - Darvish et al 2019 - report a consanguineous Afghani family with 2 children with a novel PUS7 homozygous missense variant presenting with ID, speech delay, motor impairments, and aggressive behaviour but without microcephaly and short stature.

Created: 19 May 2021, 4:47 p.m. | Last Modified: 19 May 2021, 4:47 p.m.

Panel Version: 2.176

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, OMIM:618342

Publications

• 30526862
• 30778726
• 31583274

Green List (high evidence)

11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Expert list

Created: 3 Sep 2020, 3:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, OMIM #618342

Publications

• 30526862
• 30778726
• 31583274

Variants in this GENE are reported as part of current diagnostic practice