PMC6348249_01
PMC6348249_02
PMC6348249_03
PMC6348249_04
Carboxyfluorescein succinimidyl ester lymphoproliferation assay, plot (upper panel), and indexes (lower panel).
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F3
However, CFSE lymphocyte proliferation assay was low at age 9 months, and absent 3 years later, under: PMA/ionomycin, phytohemagglutinin, concanavalin, and anti-CD3/CD28 stimuli (Figure 3).
PMC6348249_05
(A) Short stature with overweight in normocephalic school-age boy. Contrast with (B,C) Facial dysmorphisms seen in two twin sisters with LIG4 deficiency. Note prominent middle third of the face, long nose, micrognathia, long ears, jaundice, protruding tongue. (Face photos published with permission from their mothers).
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F1
In time, the patient, now 6 years old, developed obesity with normal stature and head circumference (see Figure 1), and no other manifestation. On physical examination, short stature (below percentile 10), low weight, mild to moderate mental retardation and speech delay were noted, with microcephaly below p3, a prominent mid-face with long nose, and micrognathia with a protruding tongue (see Figure 1).
Family trees. In Family A, the elder siblings of the proband died young of lymphoma. The proband has a history of avascular necrosis of the femoral head, short stature and isolated CD4+ deficiency; his younger brother is asymptomatic. In Family B, teenage twin sisters died after a long history of recurrent infections, chronic liver disease, and progressive bone marrow failure (The pedigrees were built at pedigree.progenygenetics.com; they are included after written informed consent from the mothers).
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F2
A younger brother, born in 2017, is also asymptomatic, in apparent good health (Figure 2).
PMC6348249_06