TY - JOUR
T1 - Variants in PHF8 cause a spectrum of X-linked neurodevelopmental disorders and facial dysmorphology
AU - University of Washington Center for Mendelian Genomics
AU - Sobering, Andrew K.
AU - Bryant, Laura M.
AU - Li, Dong
AU - McGaughran, Julie
AU - Maystadt, Isabelle
AU - Moortgat, Stephanie
AU - Graham, John M.
AU - van Haeringen, Arie
AU - Ruivenkamp, Claudia
AU - Cuperus, Roos
AU - Vogt, Julie
AU - Morton, Jenny
AU - Brasch-Andersen, Charlotte
AU - Steenhof, Maria
AU - Hansen, Lars Kjærsgaard
AU - Adler, Élodie
AU - Lyonnet, Stanislas
AU - Pingault, Veronique
AU - Sandrine, Marlin
AU - Ziegler, Alban
AU - Donald, Tyhiesia
AU - Nelson, Beverly
AU - Holt, Brandon
AU - Petryna, Oleksandra
AU - Firth, Helen
AU - McWalter, Kirsty
AU - Zyskind, Jacob
AU - Telegrafi, Aida
AU - Juusola, Jane
AU - Person, Richard
AU - Bamshad, Michael J.
AU - Earl, Dawn
AU - Tsai, Anne Chun Hui
AU - Yearwood, Katherine R.
AU - Marco, Elysa
AU - Nowak, Catherine
AU - Douglas, Jessica
AU - Hakonarson, Hakon
AU - Bhoj, Elizabeth J.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7/14
Y1 - 2022/7/14
N2 - Loss-of-function variants in PHD Finger Protein 8 (PHF8) cause Siderius X-linked intellectual disability (ID) syndrome, hereafter called PHF8-XLID. PHF8 is a histone demethylase that is important for epigenetic regulation of gene expression. PHF8-XLID is an under-characterized disorder with only five previous reports describing different PHF8 predicted loss-of-function variants in eight individuals. Features of PHF8-XLID include ID and craniofacial dysmorphology. In this report we present 16 additional individuals with PHF8-XLID from 11 different families of diverse ancestry. We also present five individuals from four different families who have ID and a variant of unknown significance in PHF8 with no other explanatory variant in another gene. All affected individuals exhibited developmental delay and all but two had borderline to severe ID. Of the two who did not have ID, one had dyscalculia and the other had mild learning difficulties. Craniofacial findings such as hypertelorism, microcephaly, elongated face, ptosis, and mild facial asymmetry were found in some affected individuals. Orofacial clefting was seen in three individuals from our cohort, suggesting that this feature is less common than previously reported. Autism spectrum disorder and attention deficit hyperactivity disorder, which were not previously emphasized in PHF8-XLID, were frequently observed in affected individuals. This series expands the clinical phenotype of this rare ID syndrome caused by loss of PHF8 function.
AB - Loss-of-function variants in PHD Finger Protein 8 (PHF8) cause Siderius X-linked intellectual disability (ID) syndrome, hereafter called PHF8-XLID. PHF8 is a histone demethylase that is important for epigenetic regulation of gene expression. PHF8-XLID is an under-characterized disorder with only five previous reports describing different PHF8 predicted loss-of-function variants in eight individuals. Features of PHF8-XLID include ID and craniofacial dysmorphology. In this report we present 16 additional individuals with PHF8-XLID from 11 different families of diverse ancestry. We also present five individuals from four different families who have ID and a variant of unknown significance in PHF8 with no other explanatory variant in another gene. All affected individuals exhibited developmental delay and all but two had borderline to severe ID. Of the two who did not have ID, one had dyscalculia and the other had mild learning difficulties. Craniofacial findings such as hypertelorism, microcephaly, elongated face, ptosis, and mild facial asymmetry were found in some affected individuals. Orofacial clefting was seen in three individuals from our cohort, suggesting that this feature is less common than previously reported. Autism spectrum disorder and attention deficit hyperactivity disorder, which were not previously emphasized in PHF8-XLID, were frequently observed in affected individuals. This series expands the clinical phenotype of this rare ID syndrome caused by loss of PHF8 function.
KW - PHF8
KW - X-linked intellectual disability
KW - epigenetic gene regulation
KW - histone demethylation
KW - orofacial clefting
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U2 - 10.1016/j.xhgg.2022.100102
DO - 10.1016/j.xhgg.2022.100102
M3 - Article
AN - SCOPUS:85128325995
SN - 2666-2477
VL - 3
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
IS - 3
M1 - 100102
ER -