10q26.1 Microdeletion: Redefining the critical regions for microcephaly and genital anomalies

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 11; pp. 2707 - 2713
• Main Authors: Choucair, Nancy, Abou Ghoch, Joelle, Fawaz, Ali, Mégarbané, André, Chouery, Eliane
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2015; Wiley Subscription Services, Inc
• Subjects: Child; chromosomal microarray analysis; Chromosome Deletion; Chromosomes, Human, Pair 10 - genetics; critical region; genital anomalies; growth; Humans; Infant; Infant, Newborn; intellectual disability; interstitial deletion; Male; microcephaly; Microcephaly - complications; Microcephaly - genetics; monosomy 10q; Oligonucleotide Array Sequence Analysis; psychomotor retardation; Urogenital Abnormalities - complications; Urogenital Abnormalities - genetics; microcephaly; psychomotor retardation; interstitial deletion; monosomy 10q; growth; critical region; genital anomalies; intellectual disability; chromosomal microarray analysis
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37211

Distal 10q deletion syndrome is a well‐characterized chromosomal disorder consisting of neurodevelopmental impairment, facial dysmorphism, cardiac malformations, genital and urinary tract defects, as well as digital anomalies. Patients with interstitial deletions involving band 10q26.1 present a phenotype similar to the ones with the distal 10q deletion syndrome, which led to the definition of a causal 600 kb smallest region of overlap (SRO). In this report, we describe a male patient with an interstitial 4.5 Mb deletion involving exclusively the 10q26.1 segment. He had growth and psychomotor retardation, microcephaly, flat feet, micropenis, and cryptorchidism. The patient's deleted region does not overlap the 10q SRO. We reviewed the clinical phenotype of patients with similar deletions and suggest the presence of two new SROs, one associated with microcephaly, growth and psychomotor retardation, and the other associated to genital anomalies. Interestingly, we narrowed those regions to segments encompassing five and two genes, respectively. FGFR2, NSMCE4A, and ATE1 were suggested as candidates for facial dysmorphism, growth cessation, and heart defects, respectively. WDR11 was linked to idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Its haploinsufficiency could play a crucial role in the genital anomalies of these patients. © 2015 Wiley Periodicals, Inc.