Universität zu Köln

Zweier, Christiane ORCID: 0000-0001-8002-2020, Kraus, Cornelia, Brueton, Louise, Cole, Trevor, Degenhardt, Franziska, Engels, Hartmut, Gillessen-Kaesbach, Gabriele, Graul-Neumann, Luitgard, Horn, Denise, Hoyer, Juliane, Just, Walter, Rauch, Anita ORCID: 0000-0003-2930-3163, Reis, Andre ORCID: 0000-0002-6301-6363, Wollnik, Bernd, Zeschnigk, Michael, Luedecke, Hermann-Josef and Wieczorek, Dagmar ORCID: 0000-0003-2812-6492 (2013). A new face of Borjeson-Forssman-Lehmann syndrome? De novo mutations in PHF6 in seven females with a distinct phenotype. J. Med. Genet., 50 (12). S. 838 - 848. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-6244

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Abstract

Background Borjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked recessive intellectual disability (ID) disorder caused by mutations in the PHF6 gene and characterised by variable cognitive impairment, a distinct facial gestalt, obesity, and hypogonadism. Female carriers are usually not affected or only mildly affected, and so far only two females with de novo mutations or deletions in PHF6 have been reported. Methods and results We performed PHF6 mutational analysis and screening for intragenic deletions and duplications by quantitative real-time PCR and multiplex ligation dependent probe amplification (MLPA) in female patients with variable ID and a distinct appearance of sparse hair, remarkable facial features, hypoplastic nails, and teeth anomalies. We detected two truncating mutations and two duplications of exons 4 and 5. Furthermore, two female patients with PHF6 deletions and a similar phenotype were identified by routine molecular karyotyping. Recently, two patients with a clinical diagnosis of Coffin-Siris syndrome in early infancy had been found to harbour mutations in PHF6, and their phenotype in advanced ages is now described. Further studies revealed skewed X-inactivation in blood lymphocytes, while it was normal in fibroblasts, thus indicating functional mosaicism. Conclusions Our findings indicate that de novo defects in PHF6 in females result in a recognisable phenotype which might have been under-recognised so far and which comprises variable ID, a characteristic facial gestalt, hypoplastic nails, brachydactyly, clinodactyly mainly of fingers IV and V, dental anomalies, and linear skin hyperpigmentation. It shows overlap with BFLS but also additional distinct features, thus adding a new facet to this disorder.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zweier, Christiane UNSPECIFIED orcid.org/0000-0001-8002-2020 UNSPECIFIED Kraus, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Brueton, Louise UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, Trevor UNSPECIFIED UNSPECIFIED UNSPECIFIED Degenhardt, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Engels, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Gillessen-Kaesbach, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Graul-Neumann, Luitgard UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyer, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Just, Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauch, Anita UNSPECIFIED orcid.org/0000-0003-2930-3163 UNSPECIFIED Reis, Andre UNSPECIFIED orcid.org/0000-0002-6301-6363 UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeschnigk, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Luedecke, Hermann-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieczorek, Dagmar UNSPECIFIED orcid.org/0000-0003-2812-6492 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-471209
DOI:	10.1136/jmedgenet-2013-101918
Journal or Publication Title:	J. Med. Genet.
Volume:	50
Number:	12
Page Range:	S. 838 - 848
Date:	2013
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-6244
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHROMATIN-REMODELING COMPLEX; FINGER; ARID1B Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47120