HNRNPH1-related syndromic intellectual disability: Seven additional cases suggestive of a distinct syndromic neurodevelopmental syndrome.
HNRNPH1 gene
congenital abnormalities
intellectual disability
microcephaly
whole exome sequencing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
28
02
2020
revised:
13
04
2020
accepted:
22
04
2020
pubmed:
27
4
2020
medline:
7
7
2021
entrez:
27
4
2020
Statut:
ppublish
Résumé
Pathogenic variants in HNRNPH1 were first reported in 2018. The reported individual, a 13 year old boy with a c.616C>T (p.R206W) variant in the HNRNPH1 gene, was noted to have overlapping symptoms with those observed in HNRNPH2-related X-linked intellectual disability, Bain type (MRXSB), specifically intellectual disability and dysmorphic features. While HNRNPH1 variants were initially proposed to represent an autosomal cause of MRXSB, we report an additional seven cases which identify phenotypic differences from MRXSB. Patients with HNRNPH1 pathogenic variants diagnosed via WES were identified using clinical networks and GeneMatcher. Features unique to individuals with HNRNPH1 variants include distinctive dysmorphic facial features; an increased incidence of congenital anomalies including cranial and brain abnormalities, genitourinary malformations, and palate abnormalities; increased incidence of ophthalmologic abnormalities; and a decreased incidence of epilepsy and cardiac defects compared to those with MRXSB. This suggests that pathogenic variants in HNRNPH1 result in a related, but distinct syndromic cause of intellectual disability from MRXSB, which we refer to as HNRNPH1-related syndromic intellectual disability.
Substances chimiques
Heterogeneous-Nuclear Ribonucleoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
91-98Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Han SP, Tang YH, Smith R. Functional diversity of the hnRNPs: past, present and perspectives. Biochem J. 2010;430(3):379-392.
Honore B, Rasmussen HH, Vorum H, et al. Heterogeneous nuclear ribonucleoproteins H, H', and F are members of a ubiquitously expressed subfamily of related but distinct proteins encoded by genes mapping to different chromosomes. J Biol Chem. 1995;270(48):28780-28789.
Van Dusen CM, Yee L, McNally LM, McNally MT. A glycine-rich domain of hnRNP H/F promotes nucleocytoplasmic shuttling and nuclear import through an interaction with Transportin 1. Mol Cell Biol. 2010;30(10):2552-2562.
Geuens T, Bouhy D, Timmerman V. The hnRNP family: insights into their role in health and disease. Hum Genet. 2016;135(8):851-867.
Au PYB, You J, Caluseriu O, et al. GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial Dysmorphisms, and skeletal and connective tissue abnormalities caused by De novo variants in HNRNPK. Hum Mutat. 2015;36(10):1009-1014.
Bain Jennifer M, Cho Megan T, Telegrafi A, et al. Variants in HNRNPH2 on the X chromosome are associated with a neurodevelopmental disorder in females. Am J Hum Genet. 2016;99(3):728-734.
Bramswig NC, Lüdecke H-J, Hamdan FF, et al. Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability. Hum Genet. 2017;136(7):821-834.
Harmsen S, Buchert R, Mayatepek E, Haack TB, Distelmaier F. Bain type of X-linked syndromic mental retardation in boys. Clin Genet. 2019;95(6):734-735.
Jepsen WM, Ramsey K, Szelinger S, et al. Two additional males with X-linked, syndromic mental retardation carry de novo mutations in HNRNPH2. Clin Genet. 2019;96(2):183-185.
Somashekar PH, Narayanan DL, Jagadeesh S, et al. Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2. Am J Med Genet A. 2020;182(1):183-188.
Pilch J, Koppolu AA, Walczak A, et al. Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation. Clin Genet. 2018;94(3-4):381-385.
Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36(10):928-930.
Yang J, Kim O, Wu J, Qiu Y. Interaction between tyrosine kinase Etk and a RUN domain- and FYVE domain-containing protein RUFY1: a possible role of Etk in regulation of vesicle trafficking. J Biol Chem. 2002;277(33):30219-30226.