{Reference Type}: Journal Article
{Title}: Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases.
{Author}: Levy M;Elron E;Shohat M;Lifshitz S;Kahana S;Shani H;Grossman A;Amar S;Narkis G;Sagi-Dain L;Basel-Salmon L;Maya I;
{Journal}: J Hum Genet
{Volume}: 69
{Issue}: 7
{Year}: 2024 Jul 18
{Factor}: 3.755
{DOI}: 10.1038/s10038-024-01252-7
{Abstract}: BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.