Monogenic short stature

Gene: MRAS

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains AMBER

Created: 31 Jan 2023, 5:28 p.m. | Last Modified: 31 Jan 2023, 5:28 p.m.

Panel Version: 2.33

Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)

Created: 5 Oct 2022, 4:56 p.m. | Last Modified: 5 Oct 2022, 4:56 p.m.

Panel Version: 1.110

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (confirmed).

PMID: 28289718. 2 patients with a clinical diagnosis of Noonan syndrome were reported. Case 1: 15 yo girl with biventricular HCM that presented in infancy. She had short stature, facial dysmorphisms, global DD and cognitive disability. Parents are unaffected.
Case 2: 6 yo girl with cardiac hypertrophy, pulmonary valve stenosis, atrial septal defect, facial dysmorphisms, ptosis and DD. Both patients had de novo missense variants.

PMID: 31173466. 3 yo Japanese boy. Diagnosed with HCM during neonatal period, bilateral sensoineural hearing impairment, difficulty feeding at 4 months (poor weight gain), short stature, relative macrocephaly, height at 1 year 3 months was -3.0 SD, facial dysmorphisms. Patient had de novo missense variant.

PMID: 31108500. Case 1: North African Jewish descent. Birth length -1.1 SD, birth weight -1.1 SD. 14 months LV HCM. 15 months growth delay (height and weight -2.0 SD). Moderate hearing loss, mild global DD, GH deficiency. 2 years 3 months, height and weight was -2.0 SD and OCF +1.0 SD, facial dysmorphisms (suggestive of NS). Case 2: Germany. HCM, facial dysmorphisms and short neck.

PMID: 34080768. HCM at birth and facial dysmorphisms.

While there are >3 unrelated cases the patients in the article did not meet the criteria set out for this panel. This gene has been given an Amber rating for now.

Created: 30 Sep 2021, 2:52 p.m. | Last Modified: 30 Sep 2021, 2:52 p.m.

Panel Version: 1.78

Green List (high evidence)

Other Rasopathy genes included in this panel. At least 6 unrelated individuals reported.
Sources: Expert Review

Created: 14 Aug 2021, 5:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome 11, MIM#618499

Publications

• 28289718
• 31173466
• 31108500
• 31173466