PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals

• DOI: 10.3389/fcell.2022.1020609
• Publication Date: 2023-01-16T18:00:50Z
• Authors: Antje Kampmeier; Elsa Leitão; Ilaria Parenti; Jasmin Beygo; Christel Depienne; Nuria C Bramswig; Tzung-Chien Hsieh; Alexandra Afenjar; Stefanie Beck-Wödl; Ute Grasshoff; Tobias B Haack; Emilia K Bijlsma; Claudia Ruivenkamp; Eva Lausberg; Miriam Elbracht; Maria K Haanpää; Hannele Koillinen; Uwe Heinrich; Imma Rost; Rami Abou Jamra; Denny Popp; Margarete Koch-Ho...; Kevin Rostasy; Vanesa López-Gonz...; María José Sanche...; Catarina Macedo; Ariane Schmetz; Carmen Steinborn; Sabine Weidensee; Hellen Lesmann; Felix Marbach; Pilar Caro; Christian P. Schaaf; Peter Krawitz; Dagmar Wieczorek; Frank J Kaiser; Alma Kuechler
• Keywords: Sanger sequencing; Haploinsufficiency; Loss function

In 2016 and 2018, Chung, Jansen others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) mainly characterized developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism obesity (CHUJANS, #617991). So far, alterations appear to be rare cause DD/ID. “Omics” technologies such as exome sequencing or array analyses have led the identification distinct types , including, truncating variants, missense substitutions, splice variants large deletions encompassing portions gene entire well adjacent genomic regions. We collected clinical genetic data 23 individuals with -associated Chung-Jansen (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR Fluorescence-in-situ-Hybridization) segregation analysis showed either de novo occurrence inheritance an also (mildly) affected parent. accordance previously patients, almost reported here show (22/23), ID abnormalities (20/23), weight problems (13/23) characteristic craniofacial features (i.e. ears/earlobes, prominent eyebrows, anteverted nares long philtrum (23/23)). To further investigate gestalt CHUJANS, we performed using GestaltMatcher approach. By this, could establish that patients are indistinguishable based on type alteration missense, loss-of-function, site) but significant difference average face healthy Prader-Willi (PWS, #176270) CUL4B -alteration (Intellectual disorder, X-linked, syndromic, Cabezas type, #300354). Our findings expand mutational spectrum CHUJANS. discuss molecular in comparison published individuals. The fact some were inherited mildly parent illustrates variability associated phenotype outlines importance thorough evaluation combined for accurate diagnosis counselling.