Figure 2.

Bi-allelic TUBGCP2 Variants in Families 2, 3, and 4

(A) Family 2 with an affected proband born to parents from India with no historical evidence for consanguinity. The genotype of the variant in TUBGCP2 in the proband (individual II-3 [Family 2]) was determined based on exome sequencing and parental genotypes confirmed by Sanger sequencing.

(B–I) T2 weighted brain MRI images in individual II-3 (Family 2) at 4 weeks (B–E) and at 5 months of age (F–I). Progression of the disease was shown by loss of white matter, thinning of corpus callosum (arrow in H), volume loss of pons, and exuberant subependymal cyst formation (arrow in I) at 5 months of age.

(J) Family 3 with an affected proband born to consanguineous parents from Iran. Note that the homozygous variant in TUBGCP2 identified in this family was the same variant identified in Family 2.

(K and L) Individual II-2 (Family 3) showing microcephaly, synophrys, micrognathia, and hypoplastic maxilla.

(M–O) Brain MRI of individual II-2 (Family 3) at 1 year of age showed pachygyria, hyperintense periventricular white matter, very thin corpus callosum, and subependymal cysts (arrow in O).

(P) Family 4 with an affected proband born to non-consanguineous parents from Poland. The DNA sequences shown in upper case denote coding sequences, whereas sequences in lower case denote the non-coding (intronic) region.

(Q and R) Individual II-1 (Family 4) showing microcephaly.

(S–U) Brain MRI of individual II-1 (Family 4) at 8 years of age shows pachygyria in the temporal lobes and partial thinning of the corpus callosum.