© 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.
|Number of pages||5|
|Publication status||Published - 1 Jun 2018|
Bibliographical noteFunding Information:
We thank to this family for their continuous cooperation. This work was supported by PAICYT (SA-105-15) and CONACYT (INFRA-2013-204423, INFRA-2016-268123; S0008-2014-1-233212) for C.C.-F. M.M.R.-S. was supported by a CONACYT scholarship. We would also like to thank Dr H. Rivera for revision of this manuscript.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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