A 30 Mainland Chinese cohort of patients with Phelan-McDermid syndrome:
genotype-phenotype correlation and the role of SHANK3 haploinsufficiency
in the important phenotypes
Abstract
This is the first study describing a cohort of Mainland China patients
broaden the clinical and molecular spectrum of Phelan-McDermid syndrome
(PMS) or 22q13 deletion syndrome. A total of 30 Mainland China patients
were clinically and genetically evaluated. We discover that nineteen
patients with 22q13.3 deletions, one patient with terminal deletions and
duplications, one patient with duplications, and nine patients with
SHANK3 mutations were included. Six novel heterozygous variants,
c.3838_3839insGG, c.3088delC, c.3526G>T, c.3372dupC,
c.3120delC and c.3942delC, were firstly reported. Besides, we
demonstrated speech delay, DD/ID, ASD, hypotonia and hyperactivity were
prominent clinical features. Since most reported cases used to
genotype-phenotype analyses are caused by 22q13 deletions usually
encompassing many genes including SHANK3, we performed
genotype-phenotype analysis, and found hypotonia was 100% of cases with
loss of SHANK3 alone and there was no significant difference between
loss of SHANK3 alone and deletions encompass more than SHANK3 gene
regarding hypotonia, DD/ID, ASD, increased pain tolerance, gait
abnormalities, impulsiveness, repetitive behaviors, regression and
nonstop crying which are high frequency in loss of SHANK3 alone group.
This analysis improves the understanding that SHANK3 haploinsufficiency
is a major contributor to the neurological phenotypes of PMS and also
responsible for other important phenotypes such as hypotonia.