Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome

Table 1

Clinical features of two patients with CdLS.

	Patient 1	Patient 2
Mutation	c.5329-15A>G	c.6344(−13)_(−8)del
Predicted effect on protein	p.(Ile1777_Arg1809del)	p.(Gly2115Valfs11)
Clinical severity	Mild	Severe
Gender	Male	Female
Anthropometric data (newborn)
Gestational age	41 weeks	36 weeks
Birth weight	3260 g (−0.55 SD)	2130 g (−1.01 SD)
Birth length	50 cm (−0.46 SD)	43 cm (−1.73 SD)
Birth OFC	34 cm (−1.02 SD)	30 cm (−1.71 SD)
Intrauterine growth restriction	−	+
Anthropometric data (last evaluation)
Age at evaluation	7 years	1 year
Weight at evaluation	19 kg (−1.31 SD)	4630 g (−4.74 SD)
Length at evaluation	112 cm (−2.14 SD)	63 cm (−4.61 SD)
OFC at evaluation	47 cm (−4.07 SD)	39 cm (−6.05 SD)
Postnatal growth retardation	+	+
Limb defects	Small hands, single palmar crease, short 1st metacarpal	Small hands, brachymesophalangy V, restriction of the elbow movements
Developmental delay	+; Speech delay	+; No speech; Learned walking at 3.5 years
Intellectual disability	+	+
Microcephaly	+	+
Behaviour impairment	−	+
GERD	−	+; Floppy Nissen fundoplication
Feeding and swallowing disorders	+	+; No chewing; Stomach tube until 5 years
Hirsutism	−	+
Cutis marmorata	−	+
GU anomalies	Shawl scrotum, micropenis hypospadias	NA
Others		Recurrent infections; Nuchal cystic hygroma/nuchal edema

+: present; −: not present; OFC: head circumference; CNS: central nervous system; NA: not available; GERD: gastroesophageal reflux disease; GU: genitourinary; SD: standard deviation.