%0 Journal Article
%T Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases.
%A Levy M
%A Elron E
%A Shohat M
%A Lifshitz S
%A Kahana S
%A Shani H
%A Grossman A
%A Amar S
%A Narkis G
%A Sagi-Dain L
%A Basel-Salmon L
%A Maya I
%J J Hum Genet
%V 69
%N 7
%D 2024 Jul 18
%M 38632380
%F 3.755
%R 10.1038/s10038-024-01252-7
%X <B>BACKGROUND: </B>Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance.<BR><B>METHODS: </B>We identified cases of distal Xq28 duplication (chrX: 154,126,575-154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication.<BR><B>RESULTS: </B>Our search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200-300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males.<BR><B>CONCLUSIONS: </B>Our study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.