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Table 1 Growth and development

From: Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly

  Family
  Family 1 Family 2
Ethnicity Roma (Polish) Arab (Saudi)
COPB1 variant NM_016451.4: c957+1G>T (homozygous)
GRCh37:g.14504577C>A
NM_016451.4: c.1651T>G p.(Phe551Val)
(homozygous)
GRCh37:g.14496127A>C
Patient ID IV2 IV3 IV7 IV8 IV9 IV4
Sex F F F F F F
Age at physical assessment 14y 16y 15y 15y 11y 7y
OFC − 2.6 SD − 3.2 SD − 2 SD − 0.2 SD − 7.9 SD − 4.4 SD
Weight + 2.4 SD + 2.8 SD − 3.1 SD − 2.8 SD − 3.9 SD − 3.2 SD
Height − 0.1 SD − 1.9 SD − 1.8 SD − 1.2 SD + 0.6SD − 2.2 SD
Neonatal issues Hypotonia, torticollis Hypotonia Unknown Unknown Unknown Unknown
Other genetic findings Normal microcephaly and cataract panels
Balanced 12;13 insertional translocation
Normal microcephaly and cataract panels
Unbalanced 12;13 insertional translocation (761 Kb duplication of 13q13.3)
Homozygous for GJB2 c.71G>A
Normal immunodeficiency gene panel Normal immunodeficiency gene panel Normal immunodeficiency gene panel Normal immuno-deficiency gene panel
Normal array CGH
Early development Smiled at 13m
Sat at m
Walking at 5y
First words 3y
Smiled at 13m
Sat at 12m
Walking at 4y
Early milestones not available
Cannot walk
Early milestones not available
Cannot walk
Early milestones not available
Cannot walk
Early milestones not available
Cannot walk
Age at last developmental assessment 18y 16y 17y 15y 11y 11y
Intellectual disability Severe Severe Severe Severe Severe Severe
Language and hearing Short phrases (unclear language)
Follows simple instructions
GJB2-associated deafness
No speech
Difficulty expressing needs
No speech Language “fair” No speech Limited speech
Gross motor Can go up stairs
Cannot climb
Difficulty on stairs
Poor balance
Uses wheelchair Uses wheelchair Unable to sit or stand Unable to sit or stand
Social development and behaviour Unable to perform self-care
Poor safety awareness
Intermittent incontinence (mostly urinary)
Unable to perform self-care
Incontinent of urine and faeces
Fully dependant Fully dependant Fully dependant Fully dependant
  1. Shows subjects’ growth and development. Five of six subjects had microcephaly (− 2 SD); 3/6 had severe microcephaly (> 3SD). Patients in Family 1 developed disproportionate weight to height and a “metabolic syndrome” phenotype (see Table 2). In contrast, in Family 2, subjects were underweight. All participants have a severe intellectual disability. Gross motor abilities are variable with one participant in family 1 able to walk up stairs and two participants in Family 2 unable to sit