Fig. 1: Pedigrees, photographs, and brain imaging of individuals with biallelic NSRP1 loss-of-function (LoF) variants. | Genetics in Medicine

Fig. 1: Pedigrees, photographs, and brain imaging of individuals with biallelic NSRP1 loss-of-function (LoF) variants.

From: Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy

Fig. 1

(a) Pedigree of family 1, a consanguineous family from Egypt. The proband, BAB13228, is indicated with a black arrow. B-allele frequency for BAB13228 calculated from exome variant data is shown below the pedigree and demonstrates a 3.1-Mb block of absence of heterozygosity (AOH) on chromosome 17 (gray) around NSRP1 variant (red line). (b) Pedigree of family 2, a consanguineous family from Iran. The proband, F799-004, is indicated with a black arrow. B-allele frequency for F799-004 calculated from exome variant data is shown below the pedigree and demonstrates a 7.7-Mb block of AOH on chromosome 17 (gray) around NSRP1 variant (red line). (c) Pedigree of family 3, a family from Pakistan. The proband, BAB14701, is indicated with a black arrow. B-allele frequency for affected sibling BAB14708 calculated from exome variant data demonstrates a 6.9-Mb block of AOH on chromosome 17 (gray) around NSRP1 variant (red line). (d–f) BAB13228 (family 1) at 1 year of age showing microcephaly, appendicular spasticity, clenched fists, long face with prominent chin, high forehead, prominent metopic suture, sparse hair and eyebrows, hypertelorism, broad depressed nasal bridge, upturned nose, long philtrum, V-shaped upper lip, large and low set ears, and overriding digits. (g) F799-003 at 9 years of age showing microcephaly, appendicular spasticity, high forehead, tented mouth, short philtrum, high arched palate, downslanting palpebral fissures, and simplified, prominent ears. (h) F799-004 at 3 years of age showing microcephaly, appendicular spasticity, clenched fists, high forehead, tented mouth, short philtrum, high arched palate, downslanting palpebral fissures, and simplified, prominent ears. (i–l) Representative brain magnetic resonance image (MRI) findings for BAB13228 (family 1) at four months of age. Representative axial T2 (i–k) and sagittal T2 (l) images are shown. Imaging features include underopercularization (red arrows), an immature, simplified gyral pattern, generous extra-axial cerebrospinal fluid (CSF) spaces, inferior cerebellar vermian hypoplasia (black arrowhead), dysgenesis of the corpus callosum, paucity of deep white matter, and thin brainstem. (m–p) Representative brain MRI findings for BAB14701 (family 3) at three months of age. Representative axial T2 (m–o) and sagittal T2 (p) images are shown. Imaging features include underopercularization (red arrows), simplified gyral pattern, generous extra-axial CSF spaces, and mild superior and inferior cerebellar vermian hypoplasia (white arrowheads). (q, r) Representative brain MRI findings for F799-003 (family 2) at ten years of age. Representative axial T2 (q) and sagittal T2 (r) images are shown. Underopercularization (red arrows), mild gyral simplification, generous extra-axial CSF spaces, and left posterior plagiocephaly can be seen. (s, t) Representative brain MRI findings for BAB14706 (family 3) at three years seven months. Representative axial T2/fluid-attenuated inversion recovery (FLAIR) (s) and sagittal T1 (t) are shown. The folia of the superior cerebellar vermis are prominent (white arrowhead).

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