Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability

M. M. Rangel-Sosa, L. E. Figuera-Villanueva, I. A. González-Ramos, Y. X. Pérez-Páramo, L. A. Martínez-Jacobo, L. Arnaud-López, J. A. Nastasi-Catanese, A. M. Rivas-Estilla, K. A. Galán-Huerta, A. Rojas-Martínez, R. Ortiz-López, C. Córdova-Fletes

Research output: Contribution to journalArticle

Abstract

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.
Original languageEnglish
Pages (from-to)1229-1233
Number of pages5
JournalClinical Genetics
DOIs
Publication statusPublished - 1 Jun 2018
Externally publishedYes

Fingerprint

Exome
Intellectual Disability
Siblings
Spliceosomes
Genes
Nuclear Family
Mutation
U1 Small Nuclear Ribonucleoproteins
Phenotype
Germ-Line Mutation
Computer Simulation
Exons
Hand

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Rangel-Sosa, M. M., Figuera-Villanueva, L. E., González-Ramos, I. A., Pérez-Páramo, Y. X., Martínez-Jacobo, L. A., Arnaud-López, L., ... Córdova-Fletes, C. (2018). Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability. Clinical Genetics, 1229-1233. https://doi.org/10.1111/cge.13235
Rangel-Sosa, M. M. ; Figuera-Villanueva, L. E. ; González-Ramos, I. A. ; Pérez-Páramo, Y. X. ; Martínez-Jacobo, L. A. ; Arnaud-López, L. ; Nastasi-Catanese, J. A. ; Rivas-Estilla, A. M. ; Galán-Huerta, K. A. ; Rojas-Martínez, A. ; Ortiz-López, R. ; Córdova-Fletes, C. / Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability. In: Clinical Genetics. 2018 ; pp. 1229-1233.
@article{19d701076c444ce2b0a0e28babcff503,
title = "Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability",
abstract = "{\circledC} 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.",
author = "Rangel-Sosa, {M. M.} and Figuera-Villanueva, {L. E.} and Gonz{\'a}lez-Ramos, {I. A.} and P{\'e}rez-P{\'a}ramo, {Y. X.} and Mart{\'i}nez-Jacobo, {L. A.} and L. Arnaud-L{\'o}pez and Nastasi-Catanese, {J. A.} and Rivas-Estilla, {A. M.} and Gal{\'a}n-Huerta, {K. A.} and A. Rojas-Mart{\'i}nez and R. Ortiz-L{\'o}pez and C. C{\'o}rdova-Fletes",
year = "2018",
month = "6",
day = "1",
doi = "10.1111/cge.13235",
language = "English",
pages = "1229--1233",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",

}

Rangel-Sosa, MM, Figuera-Villanueva, LE, González-Ramos, IA, Pérez-Páramo, YX, Martínez-Jacobo, LA, Arnaud-López, L, Nastasi-Catanese, JA, Rivas-Estilla, AM, Galán-Huerta, KA, Rojas-Martínez, A, Ortiz-López, R & Córdova-Fletes, C 2018, 'Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability', Clinical Genetics, pp. 1229-1233. https://doi.org/10.1111/cge.13235

Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability. / Rangel-Sosa, M. M.; Figuera-Villanueva, L. E.; González-Ramos, I. A.; Pérez-Páramo, Y. X.; Martínez-Jacobo, L. A.; Arnaud-López, L.; Nastasi-Catanese, J. A.; Rivas-Estilla, A. M.; Galán-Huerta, K. A.; Rojas-Martínez, A.; Ortiz-López, R.; Córdova-Fletes, C.

In: Clinical Genetics, 01.06.2018, p. 1229-1233.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability

AU - Rangel-Sosa, M. M.

AU - Figuera-Villanueva, L. E.

AU - González-Ramos, I. A.

AU - Pérez-Páramo, Y. X.

AU - Martínez-Jacobo, L. A.

AU - Arnaud-López, L.

AU - Nastasi-Catanese, J. A.

AU - Rivas-Estilla, A. M.

AU - Galán-Huerta, K. A.

AU - Rojas-Martínez, A.

AU - Ortiz-López, R.

AU - Córdova-Fletes, C.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.

AB - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.

U2 - 10.1111/cge.13235

DO - 10.1111/cge.13235

M3 - Article

SP - 1229

EP - 1233

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -