PMC10174234_01
Pedigree (A) and Sanger sequencing (B). Sanger DNA sequencing confirmed the heterozygous nonsense mutation c.1159C>T (p.Q387X) in KRIT1 gene in patient 1 (IV-1), 2 (III-4), 3 (II-5), and 4 (III-3). Solid black symbol indicates patient; a slash indicates deceased individual.
fonc-13-1141488-g001.jpg
PMC10174234_02_fonc-13-1141488-g001.jpg
f1
The mother of the proband (Patient 2, III-4, 38 years old) presented with focal seizures in February 2015, cerebral MRI imaging showed a cerebral cavernous angioma in the right temporal lobe ( Figures 1A ,  2B ), and then underwent surgical treatment at the hospital. II-5, 63 years old) was diagnosed with multiple microbleeds foci by SWI ( Figure 1A ). In addition, patient 4 (III-3, 35 years old) were diagnosed with CCM several years ago and underwent surgery in hospital, but no other information is available ( Figure 1A ). Patient 5 (II-1, 57 years old) was diagnosed with multiple CCM before death and presented with hemiparesis, with imaging studies showing up to hundreds of cavernous malformations in the brain ( Figure 1A ). Patient 6 (II-3, 66 years old) was diagnosed with CCM in another hospital, but unfortunately no imaging data was available ( Figure 1A ). By analyzing the data of whole-exome sequencing, we identified a novel heterozygous nonsense mutation (NM_194454.3: c.1159C>T, p.Q387X) in exon 12 of the KRIT1 gene in the proband (Patient 1) ( Figure 1B ). This result showed that the proband's mother (Patient 2, III-4), grandfather (Patient 3, II-5), and aunt (Patient 4, III-3) carries the mutation ( Figure 1B ). Regrettably, we did not get the blood sample of patients 5 (II-1) and 6 (II-3) ( Figure 1A ).
Representing images of CCM. (A) SWI images of the proband (Patient 1, IV-1) at pre-surgery and 3 months after surgery. (B) Pre-surgery cerebral MRI images of the proband's mother (Patient 2, III-4), and SWI images at one month after surgery. Red arrow, CCM lesion. Double red arrows, surgical site.
fonc-13-1141488-g002.jpg
PMC10174234_02_fonc-13-1141488-g002.jpg
f2
The mother of the proband (Patient 2, III-4, 38 years old) presented with focal seizures in February 2015, cerebral MRI imaging showed a cerebral cavernous angioma in the right temporal lobe ( Figures 1A ,  2B ), and then underwent surgical treatment at the hospital. The SWI images of patient 2 revealed multiple cavernous angioma at one month after surgery ( Figure 2B ).
PMC10174234_02
Pedigree (A) and Sanger sequencing (B). Sanger DNA sequencing confirmed the heterozygous nonsense mutation c.1159C>T (p.Q387X) in KRIT1 gene in patient 1 (IV-1), 2 (III-4), 3 (II-5), and 4 (III-3). Solid black symbol indicates patient; a slash indicates deceased individual.
fonc-13-1141488-g001.jpg
PMC10174234_02_fonc-13-1141488-g001.jpg
f1
The mother of the proband (Patient 2, III-4, 38 years old) presented with focal seizures in February 2015, cerebral MRI imaging showed a cerebral cavernous angioma in the right temporal lobe ( Figures 1A ,  2B ), and then underwent surgical treatment at the hospital. II-5, 63 years old) was diagnosed with multiple microbleeds foci by SWI ( Figure 1A ). In addition, patient 4 (III-3, 35 years old) were diagnosed with CCM several years ago and underwent surgery in hospital, but no other information is available ( Figure 1A ). Patient 5 (II-1, 57 years old) was diagnosed with multiple CCM before death and presented with hemiparesis, with imaging studies showing up to hundreds of cavernous malformations in the brain ( Figure 1A ). Patient 6 (II-3, 66 years old) was diagnosed with CCM in another hospital, but unfortunately no imaging data was available ( Figure 1A ). By analyzing the data of whole-exome sequencing, we identified a novel heterozygous nonsense mutation (NM_194454.3: c.1159C>T, p.Q387X) in exon 12 of the KRIT1 gene in the proband (Patient 1) ( Figure 1B ). This result showed that the proband's mother (Patient 2, III-4), grandfather (Patient 3, II-5), and aunt (Patient 4, III-3) carries the mutation ( Figure 1B ). Regrettably, we did not get the blood sample of patients 5 (II-1) and 6 (II-3) ( Figure 1A ).
Representing images of CCM. (A) SWI images of the proband (Patient 1, IV-1) at pre-surgery and 3 months after surgery. (B) Pre-surgery cerebral MRI images of the proband's mother (Patient 2, III-4), and SWI images at one month after surgery. Red arrow, CCM lesion. Double red arrows, surgical site.
fonc-13-1141488-g002.jpg
PMC10174234_02_fonc-13-1141488-g002.jpg
f2
The mother of the proband (Patient 2, III-4, 38 years old) presented with focal seizures in February 2015, cerebral MRI imaging showed a cerebral cavernous angioma in the right temporal lobe ( Figures 1A ,  2B ), and then underwent surgical treatment at the hospital. The SWI images of patient 2 revealed multiple cavernous angioma at one month after surgery ( Figure 2B ).