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Page 116 Fichera et al. J Transl Genet Genom 2020;4:114-32 I http://dx.doi.org/10.20517/jtgg.2020.16

A subregion of 2.5 Mb (chr1:164,501,003-167,022,133 hg19), located proximally to the SRO (SRO-P),
adds further complexity to the observed phenotype, being more commonly associated with cardiac and
renal malformations. A third distal region of 2.7 Mb (chr1: 178.514.910-181.269.712 hg19; SRO-D) could
[1]
also contribute to intrauterine and postnatal growth retardation . Finally, deletions involving SERPINC1
(chr1: 173.872.942-173.886.516; MIM: 107300) result in low antithrombin-III activity, a risk factor for
thrombophilia. We present the detailed phenotypic and molecular description of six new cases whose
partially overlapping 1q24q25 deletions were identified by chromosome microarray analysis (CMA). Four
cases, each encompassing at least one of the three critical regions, were sporadic and identified by studying
unrelated patients with syndromic intellectual disability. The fifth case, with a 1q24.3q25.2 deletion that
did not involve any of the three critical regions, was ascertained in a newborn baby after the unexpected
detection of the same deletion in the healthy father. The latter was studied as the parent of a previous child
carrying two CNVs, neither of them located on chromosome 1, which later turned out to be both inherited
from the healthy mother.

METHODS
Clinical data
All six subjects are described in more detail in the following section and their clinical characteristics
are summarized in Table 1. Patient photographs are shown in cases where parents have consented to
publication.

Case 1
The patient was a 17-year-old male born after a previous miscarriage. At birth, his mother and father were
29 and 31 years old, respectively. He has a younger healthy brother. Family history was remarkable for
cognitive delay in the paternal lineage, not otherwise specified, and bipolar disturbance in the maternal
one. The delivery was at term with fetal distress consisting of decreased heart rate patterns and meconium-
stained amniotic fluid. Birth weight was 3,450 g (50th percentile), length was 51 cm (50th percentile), and
cranial circumference-OFC was 35 cm (25th percentile). Apgar scores were 8/9 at 1’/5’, respectively. The
perinatal period was remarkable for hypotonia and limb dyskinesia. Early motor milestones were slightly
delayed: he sat between 7 and 8 months, crawled at 12 months, and walked autonomously at 18 months.
Language and learning difficulties were noticed early. He started babbling at 18 months and language
development was delayed. At the age of 13 years, Griffiths scale scores revealed moderate ID (overall IQ:
54) with pragmatic and narrative language difficulties and social skills impairment. Physical examination
revealed craniofacial dysmorphisms including short neck with slight pterigium colli, hypoplasia of
auricles with flat helix. His OFC was 53.8 cm (25th-50th percentile). In addition, ligamentous laxity,
hyperextensibility of the finger joints, bilateral flat foot with sandal gap, bilateral genu valgus, spinal
kyphosis, and decreased lumbar lordosis were observed. A supraclavicular cartilage cyst (3-mm diameter)
was noted. Brain magnetic resonance imaging, kidney ultrasound, urinalysis, and functional blood tests
were normal. The thyroid function test gave normal results. At the age of 16 years, he was classified as
suffering from severe intellectual disability with marked repetitive movements, obsessive-compulsive traits,
apathy, and abulia with episodes of coprolalia and soliloquy, without any self-hetero-aggressive behavior.
2/12
Treatment with Risperidal or Abilify was recommended. At the age of 18 years, his height was 171 cm (<
5th percentile), weight 59.7 kg (10th-25th percentile), and OFC was 55.4 cm (25th-50th percentile). Array-
CGH revealed a 4.2-Mb deletion of 1q23.3q24.2.

Case 2
The male child was born to a 40-year-old primigravida and her 43-year-old partner. Due to the father’s
oligospermia, the couple underwent two cycles of in vitro fertilization (IVF) through ICSI (intracytoplasmic
sperm injection), which led to the conception of the patient. The delivery was normal after an unremarkable