POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

Davor Lessel; Fuki M Hisama; Katalin Szakszon; Bidisha Saha; Alexander Barrios Sanjuanelo; Bonnie A Salbert; Pamela D Steele; Jennifer Baldwin; W Ted Brown; Charles Piussan; Henri Plauchu; Judit Szilvássy; Edit Horkay; Josef Högel; George M Martin; Alan J Herr; Junko Oshima; Christian Kubisch

doi:10.1002/humu.22833

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

Standard

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome. / Lessel, Davor; Hisama, Fuki M; Szakszon, Katalin; Saha, Bidisha; Sanjuanelo, Alexander Barrios; Salbert, Bonnie A; Steele, Pamela D; Baldwin, Jennifer; Brown, W Ted; Piussan, Charles; Plauchu, Henri; Szilvássy, Judit; Horkay, Edit; Högel, Josef; Martin, George M; Herr, Alan J; Oshima, Junko; Kubisch, Christian.

In: HUM MUTAT, Vol. 36, No. 11, 11.2015, p. 1070-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lessel, D, Hisama, FM, Szakszon, K, Saha, B, Sanjuanelo, AB, Salbert, BA, Steele, PD, Baldwin, J, Brown, WT, Piussan, C, Plauchu, H, Szilvássy, J, Horkay, E, Högel, J, Martin, GM, Herr, AJ, Oshima, J & Kubisch, C 2015, 'POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome', HUM MUTAT, vol. 36, no. 11, pp. 1070-9. https://doi.org/10.1002/humu.22833

APA

Lessel, D., Hisama, F. M., Szakszon, K., Saha, B., Sanjuanelo, A. B., Salbert, B. A., Steele, P. D., Baldwin, J., Brown, W. T., Piussan, C., Plauchu, H., Szilvássy, J., Horkay, E., Högel, J., Martin, G. M., Herr, A. J., Oshima, J., & Kubisch, C. (2015). POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome. HUM MUTAT, 36(11), 1070-9. https://doi.org/10.1002/humu.22833

Vancouver

Lessel D, Hisama FM, Szakszon K, Saha B, Sanjuanelo AB, Salbert BA et al. POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome. HUM MUTAT. 2015 Nov;36(11):1070-9. https://doi.org/10.1002/humu.22833

Bibtex

@article{24fd9a07a74b4c9c91c3c6bcbc06c7a1,

title = "POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome",

abstract = "Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.",

author = "Davor Lessel and Hisama, {Fuki M} and Katalin Szakszon and Bidisha Saha and Sanjuanelo, {Alexander Barrios} and Salbert, {Bonnie A} and Steele, {Pamela D} and Jennifer Baldwin and Brown, {W Ted} and Charles Piussan and Henri Plauchu and Judit Szilv{\'a}ssy and Edit Horkay and Josef H{\"o}gel and Martin, {George M} and Herr, {Alan J} and Junko Oshima and Christian Kubisch",

note = "{\textcopyright} 2015 WILEY PERIODICALS, INC.",

year = "2015",

month = nov,

doi = "10.1002/humu.22833",

language = "English",

volume = "36",

pages = "1070--9",

journal = "HUM MUTAT",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "11",

}

RIS

TY - JOUR

T1 - POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

AU - Lessel, Davor

AU - Hisama, Fuki M

AU - Szakszon, Katalin

AU - Saha, Bidisha

AU - Sanjuanelo, Alexander Barrios

AU - Salbert, Bonnie A

AU - Steele, Pamela D

AU - Baldwin, Jennifer

AU - Brown, W Ted

AU - Piussan, Charles

AU - Plauchu, Henri

AU - Szilvássy, Judit

AU - Horkay, Edit

AU - Högel, Josef

AU - Martin, George M

AU - Herr, Alan J

AU - Oshima, Junko

AU - Kubisch, Christian

PY - 2015/11

Y1 - 2015/11

N2 - Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.

AB - Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.

U2 - 10.1002/humu.22833

DO - 10.1002/humu.22833

M3 - SCORING: Journal article

C2 - 26172944

VL - 36

SP - 1070

EP - 1079

JO - HUM MUTAT

JF - HUM MUTAT

SN - 1059-7794

IS - 11

ER -