TY - JOUR
T1 - Anticipation in a family with primary familial brain calcification caused by an SLC20A2 variant
AU - Konno, Takuya
AU - Blackburn, Patrick R.
AU - Rozen, Todd D.
AU - van Gerpen, Jay A.
AU - Ross, Owen A.
AU - Atwal, Paldeep S.
AU - Wszolek, Zbigniew K.
N1 - Publisher Copyright:
© 2018 Polish Neurological Society
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Aim of the study: To describe a family with primary familial brain calcification (PFBC) due to SLC20A2 variant showing possible genetic anticipation. Materials and methods: We conducted historical, genealogical, clinical, and radiologic studies of a family with PFBC. Clinical evaluations including neurological examination and head computed tomography (CT) scans of a proband and her father were performed. They provided additional information regarding other family members. To identify a causative gene variant, we performed whole-exome sequencing for the proband followed by segregation analysis in other affected members using direct sequencing. Results: In this family, nine affected members were identified over four generations. The proband suffered from chronic daily headache including thunderclap headache. We identified an SLC20A2 (c.509delT, p.(Leu170*)) variant in three affected members over three generations. Interestingly, the age of onset became younger as the disease passed through successive generations, suggestive of genetic anticipation. Conclusions and clinical implications: For clinical purpose, it is important to consider thunderclap headache and genetic anticipation in PFBC caused by SLC20A2 variants. Further investigation is required to validate our observation.
AB - Aim of the study: To describe a family with primary familial brain calcification (PFBC) due to SLC20A2 variant showing possible genetic anticipation. Materials and methods: We conducted historical, genealogical, clinical, and radiologic studies of a family with PFBC. Clinical evaluations including neurological examination and head computed tomography (CT) scans of a proband and her father were performed. They provided additional information regarding other family members. To identify a causative gene variant, we performed whole-exome sequencing for the proband followed by segregation analysis in other affected members using direct sequencing. Results: In this family, nine affected members were identified over four generations. The proband suffered from chronic daily headache including thunderclap headache. We identified an SLC20A2 (c.509delT, p.(Leu170*)) variant in three affected members over three generations. Interestingly, the age of onset became younger as the disease passed through successive generations, suggestive of genetic anticipation. Conclusions and clinical implications: For clinical purpose, it is important to consider thunderclap headache and genetic anticipation in PFBC caused by SLC20A2 variants. Further investigation is required to validate our observation.
KW - Anticipation
KW - Idiopathic basal ganglia calcification
KW - Primary familial brain calcification
KW - SLC20A2
UR - http://www.scopus.com/inward/record.url?scp=85045705510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045705510&partnerID=8YFLogxK
U2 - 10.1016/j.pjnns.2018.03.007
DO - 10.1016/j.pjnns.2018.03.007
M3 - Article
C2 - 29680161
AN - SCOPUS:85045705510
SN - 0028-3843
VL - 52
SP - 386
EP - 389
JO - Neurologia i neurochirurgia polska
JF - Neurologia i neurochirurgia polska
IS - 3
ER -