Novel frameshift mutation in the AHDC1 gene in a Chinese global developmental delay patient:A case report

BACKGROUND Xia–Gibbs syndrome(XGS,OMIM:615829),caused by mutations within the ATHook DNA-binding motif-containing protein 1(AHDC1)gene(OMIM:615790),located on the short arm of chromosome 1 within the cytogenetic band 1p36.11,contains five noncoding 5 exons,a single 4.9-kb coding exon,and a noncoding 3 exon.CASE SUMMARY In this case report,we diagnosed and treated a 6-mo-old girl with XGS.The primary clinical symptoms included global developmental delay,hypotonia,and mild dysmorphic features.Using high-throughput whole-exosome sequencing to sequence the patient and her parents,and the results showed a novel frameshift mutation of c.1155dupG(p.Arg386Alafs*3)in the AHDC1 gene.The paternal gene was wild type.CONCLUSION This report extends the mutation spectrum of the AHDC1 gene to provide the diagnostic basis for genetic counseling in families with XGS.

Novel mutation c.2090_2091del in neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities in an 18.5-mo-old boy:A case report

BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.

SATB2-associated syndrome caused by a novel SATB2 mutation in a Chinese boy:A case report and literature review

BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.