Figure 1.

Two Unrelated Pedigrees with Complex Syndromic Features Harbor Recessive NCAPG2 Mutations

(A) Pedigrees of two families harboring NCAPG2 missense mutations. Family 1 has one affected female with compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut). An affected female from an unrelated pedigree (family 2) inherited a homozygous missense NCAPG2 mutation, c.2548A>C (p.Thr850Pro), from carrier parents. The healthy dizygotic twin sibling of the proband is homozygous for the WT allele. Affected individuals (shaded symbols) are denoted with an arrow in each pedigree; NA = sample not available.

(B) Brain MRI without contrast (family 1 proband, 9 years of age) indicates cerebellar vermian hypoplasia (blue arrows).

(C) A renal ultrasound (US; family 1 proband, 1 year of age) shows bilateral grade I hydronephrosis (green arrows); right kidney, 4.8 cm; left kidney, 4.6 cm.

(D) A renal US (family 2 proband, 2 months of age) shows bilateral grade II hydronephrosis (green arrows); right kidney, 3.0 cm; left kidney, 2.9 cm.

(E) A radiograph (family 1 proband, 5 years of age) indicates thoracolumbar S-shaped scoliosis. L = left.

(F) A radiograph (family 2 proband, 1 month of age) shows a low-lying conus medullaris terminating at the bottom of L3; there is no evidence of a thickened filum terminale or spinal dysraphism.

(G) Radiographs (family 1 proband, 19 months of age) show bilateral polydactyly of the feet. There are 6 digits in each foot and each has a proximal, middle, and distal phalanx.

(H) Schematic of the NCAPG2 protein (GenBank: NP_060230.5) showing domain structure and localization of mutations identified in affected individuals (indicated by red arrow). Numbers indicate amino acid position; N = amino-terminus; C = carboxyl-terminus.