Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review

BACKGROUND: Xq22.1–q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1–q22.3 deletions. METHODS: Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1–q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype–phenotype correlations. RESULTS: We described a female foetus who is the “proband” of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000–105,740,000) in chromosome Xq22.1–q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1–q22.3 but to have a normal phenotype with normal intelligence. CONCLUSIONS: Our findings further improve the understanding of the genotype–phenotype correlations of chromosome Xq22.1–q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01547-2.