TY - JOUR
T1 - A novel syndrome with short stature, mandibular hypoplasia, and osteoporosis may be associated with a PRRT3 variant
AU - Garg, Abhimanyu
AU - El-Shanti, Hatem
AU - Xing, Chao
AU - Zhou, Zhengyang
AU - Abujbara, Mousa
AU - Al-Rashed, Khadeja
AU - El-Khateeb, Mohammed
AU - Ajlouni, Kamel
AU - Agarwal, Anil K.
N1 - Funding Information:
Financial Support: This work was supported by grants from the National Institutes of Health, R01-DK105448, and by the Southwestern Medical Foundation. The funding sources were not involved in study design, analysis, interpretation of data, writing of the paper, and in the decision to submit the article for publication.
Publisher Copyright:
© Endocrine Society 2020.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Context: Despite considerable progress in elucidating the molecular basis of various progeroid syndromes, some rare patients remain unexplained. Objective: To elucidate molecular genetic basis of a novel autosomal recessive progeroid syndrome. Participants: A 24-year-old male and his 18-year-old sister with short stature, mandibular hypoplasia, pointed nose, shrill voice, severe osteoporosis, and short eyebrows and their unaffected siblings and parents belonging to a consanguineous Arab family. Results: Using exome and Sanger sequencing, we report a novel homozygous p.Glu394Lys disease-causing variant in proline-rich transmembrane protein 3 (PRRT3). PRRT3 belongs to the family of proline-rich proteins containing several repeats of a short proline-rich sequence, but its function remains to be determined. Preliminary observations showing colocalization of Prrt3 and synaptophysin support its role in vesicle exocytosis. Consistent with the highest messenger ribonucleic acid expression of PRRT3 in the pituitary, both the patients had mild growth hormone deficiency but had near normal reproductive development. Conclusions: We conclude that the homozygous p.Glu394Lys variant in PRRT3 may be associated with a novel autosomal recessive, progeroid syndrome with short stature, mandibular hypoplasia, osteoporosis, short eyebrows, and mild growth hormone (GH) deficiency. Our findings extend the spectrum of progeroid syndromes and elucidate important functions of PRRT3 in human biology, including secretion of GH from the pituitary.
AB - Context: Despite considerable progress in elucidating the molecular basis of various progeroid syndromes, some rare patients remain unexplained. Objective: To elucidate molecular genetic basis of a novel autosomal recessive progeroid syndrome. Participants: A 24-year-old male and his 18-year-old sister with short stature, mandibular hypoplasia, pointed nose, shrill voice, severe osteoporosis, and short eyebrows and their unaffected siblings and parents belonging to a consanguineous Arab family. Results: Using exome and Sanger sequencing, we report a novel homozygous p.Glu394Lys disease-causing variant in proline-rich transmembrane protein 3 (PRRT3). PRRT3 belongs to the family of proline-rich proteins containing several repeats of a short proline-rich sequence, but its function remains to be determined. Preliminary observations showing colocalization of Prrt3 and synaptophysin support its role in vesicle exocytosis. Consistent with the highest messenger ribonucleic acid expression of PRRT3 in the pituitary, both the patients had mild growth hormone deficiency but had near normal reproductive development. Conclusions: We conclude that the homozygous p.Glu394Lys variant in PRRT3 may be associated with a novel autosomal recessive, progeroid syndrome with short stature, mandibular hypoplasia, osteoporosis, short eyebrows, and mild growth hormone (GH) deficiency. Our findings extend the spectrum of progeroid syndromes and elucidate important functions of PRRT3 in human biology, including secretion of GH from the pituitary.
KW - Growth
KW - Mandibular hypoplasia
KW - PRRT3
KW - Progeroid syndrome
KW - Short stature
UR - http://www.scopus.com/inward/record.url?scp=85090560611&partnerID=8YFLogxK
U2 - 10.1210/jendso/bvaa088
DO - 10.1210/jendso/bvaa088
M3 - Article
AN - SCOPUS:85090560611
SN - 2472-1972
VL - 4
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
IS - 8
M1 - bvaa088
ER -