Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome

Aida Telegrafi, Bryn D. Webb, Sarah M. Robbins, Carlos E. Speck-Martins, David Fitzpatrick, Leah Fleming, Richard Redett, Andreas Dufke, Gunnar Houge, Jeske J.T. van Harssel, Alain Verloes, Angela Robles, Irini Manoli, Elizabeth C. Engle, Ethylin W. Jabs, David Valle, John Carey, Julie E. Hoover-Fong, Nara L.M. Sobreira

Research output: Contribution to journalArticle

Abstract

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - 2017

Fingerprint

Mobius Syndrome
Muscle Hypotonia
North American Indians
Cleft Palate
Siblings
Malignant Hyperthermia
Muscular Diseases
Clubfoot
Scoliosis
Hispanic Americans

Keywords

  • Carey-Fineman-Ziter syndrome
  • Cleft palate
  • Moebius syndrome
  • Myopathy
  • Native American Myopathy
  • P.Trp284Ser variant
  • Puerto Rican
  • Qatar

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. / Telegrafi, Aida; Webb, Bryn D.; Robbins, Sarah M.; Speck-Martins, Carlos E.; Fitzpatrick, David; Fleming, Leah; Redett, Richard; Dufke, Andreas; Houge, Gunnar; van Harssel, Jeske J.T.; Verloes, Alain; Robles, Angela; Manoli, Irini; Engle, Elizabeth C.; Jabs, Ethylin W.; Valle, David; Carey, John; Hoover-Fong, Julie E.; Sobreira, Nara L.M.

In: American Journal of Medical Genetics, Part A, 2017.

Research output: Contribution to journalArticle

Telegrafi, A, Webb, BD, Robbins, SM, Speck-Martins, CE, Fitzpatrick, D, Fleming, L, Redett, R, Dufke, A, Houge, G, van Harssel, JJT, Verloes, A, Robles, A, Manoli, I, Engle, EC, Jabs, EW, Valle, D, Carey, J, Hoover-Fong, JE & Sobreira, NLM 2017, 'Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome' American Journal of Medical Genetics, Part A. DOI: 10.1002/ajmg.a.38375

Telegrafi, Aida; Webb, Bryn D.; Robbins, Sarah M.; Speck-Martins, Carlos E.; Fitzpatrick, David; Fleming, Leah; Redett, Richard; Dufke, Andreas; Houge, Gunnar; van Harssel, Jeske J.T.; Verloes, Alain; Robles, Angela; Manoli, Irini; Engle, Elizabeth C.; Jabs, Ethylin W.; Valle, David; Carey, John; Hoover-Fong, Julie E.; Sobreira, Nara L.M. / Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.

In: American Journal of Medical Genetics, Part A, 2017.

Research output: Contribution to journalArticle

@article{ed3b82af522d42819e6e1e597016f979,
title = "Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome",
abstract = "Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.",
keywords = "Carey-Fineman-Ziter syndrome, Cleft palate, Moebius syndrome, Myopathy, Native American Myopathy, P.Trp284Ser variant, Puerto Rican, Qatar",
author = "Aida Telegrafi and Webb, {Bryn D.} and Robbins, {Sarah M.} and Speck-Martins, {Carlos E.} and David Fitzpatrick and Leah Fleming and Richard Redett and Andreas Dufke and Gunnar Houge and {van Harssel}, {Jeske J.T.} and Alain Verloes and Angela Robles and Irini Manoli and Engle, {Elizabeth C.} and Jabs, {Ethylin W.} and David Valle and John Carey and Hoover-Fong, {Julie E.} and Sobreira, {Nara L.M.}",
year = "2017",
doi = "10.1002/ajmg.a.38375",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",

}

TY - JOUR

T1 - Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome

AU - Telegrafi,Aida

AU - Webb,Bryn D.

AU - Robbins,Sarah M.

AU - Speck-Martins,Carlos E.

AU - Fitzpatrick,David

AU - Fleming,Leah

AU - Redett,Richard

AU - Dufke,Andreas

AU - Houge,Gunnar

AU - van Harssel,Jeske J.T.

AU - Verloes,Alain

AU - Robles,Angela

AU - Manoli,Irini

AU - Engle,Elizabeth C.

AU - Jabs,Ethylin W.

AU - Valle,David

AU - Carey,John

AU - Hoover-Fong,Julie E.

AU - Sobreira,Nara L.M.

PY - 2017

Y1 - 2017

N2 - Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.

AB - Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.

KW - Carey-Fineman-Ziter syndrome

KW - Cleft palate

KW - Moebius syndrome

KW - Myopathy

KW - Native American Myopathy

KW - P.Trp284Ser variant

KW - Puerto Rican

KW - Qatar

UR - http://www.scopus.com/inward/record.url?scp=85026762148&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026762148&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.38375

DO - 10.1002/ajmg.a.38375

M3 - Article

JO - American Journal of Medical Genetics, Part A

T2 - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

ER -