A Palindrome-Like Structure on 16p13.3 Is Associated with the Formation of Complex Structural Variations and SRRM2 Haploinsufficiency

Table 1

Comparison of genetic and clinical details between 6 individuals from the 100K Genomes Project with loss of function variants in SRRM2 and the 22 cases reported previously.

	Cases reported here ()	Cases reported by [9] ()
SRRM2 variant type	1 frameshift, 1 nonsense, 4 microdeletions (3 complexes)	12 frameshifts, 8 nonsenses, 2 microdeletions
Inheritance	de novo in 5/6†	de novo in 19/22
Prevalence	5/6517 in ID cases from 100kGP (v15 26th May 2022)	2/1000 in the discovery cohort
Gender	3 M, 3 F	14 M, 8 F
Ethnicity	6/6 white	NA
Age at last assessment	5-16 y	4-28 y ()
Phenotype blending	2/6	NA
Developmental delay	6/6	22/22
Language delay	6/6	16/19
Walking delay	6/6 (1 mild)	8/22
Intellectual disability	6/6 (moderate to severe)	16/20
Seizures	2/6	Not reported
Microcephaly	3/6	1/22 (also 2 with macrocephaly)
Autistic features	4/6	9/22
ADHD features	5/6	6/22
Hypersociability/friendliness	3/6	8/22
Anxiety	3/6	2/22
Hyperphagia	2/6	4/22
Feeding difficulties	4/6	5/22
Neonatal hypotonia	4/6	4/22
Hypotonia at the last assessment	2/6 (also 1 with increased tone)	9/22
Dystonia	2/6	NA
Coordination trouble/dyspraxia	4/6	5/22
Overweight	2/6	12/22
Obesity	1/6	7/22
Tall stature	2/6	4/22
Facial dysmorphism	6/6	20/22
Geographic tongue	2/6‡	NA
Small/short hands and feet	2/5	6/22
Scoliosis	2/6 (1 mild)	1/22 (with hemivertebra)
Planovalgus	2/6	NA
Strabismus	2/6	4/22
Hypermetropia	1/6	3/22
Kidney anomaly	1/3 (L-hydronephrosis and 2 renal cysts)	1/22 (unilateral hypoplastic kidney)
Micropenis/small testes	1/3 (absent testis)	1/14 (both)

†For P3, de novo status is inferred by haplotype analysis (Figure 2). ‡Shown for P3 in Figure 3(a).